Translate this page to:
In JoVE (1)
Other Publications (198)
- Anatomical Sciences Education
- Blood
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- Journal of the American College of Cardiology
- Proceedings of the National Academy of Sciences of the United States of America
- Psychiatric Services (Washington, D.C.)
- Pediatric Dermatology
- BMC Psychiatry
- Biology Letters
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- Conservation Biology : the Journal of the Society for Conservation Biology
- Methods in Molecular Biology (Clifton, N.J.)
- Journal of Neuroengineering and Rehabilitation
- International Journal of Mental Health Systems
- Environmental Science & Technology
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- General Hospital Psychiatry
- Evolution; International Journal of Organic Evolution
- Journal of Combinatorial Chemistry
- Clinical Anatomy (New York, N.Y.)
- Physical Therapy
- Journal of Affective Disorders
- Journal of Affective Disorders
- Physical Chemistry Chemical Physics : PCCP
- Journal of Affective Disorders
- Journal of Affective Disorders
- Journal of Affective Disorders
- Journal of Affective Disorders
- Pain
- Blood
- Clinical Genitourinary Cancer
- Psychology, Health & Medicine
- Epidemiologia E Psichiatria Sociale
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- International Journal of Methods in Psychiatric Research
- Depression and Anxiety
- Applied and Environmental Microbiology
- Circulation. Heart Failure
- Cancer
- Psychiatric Services (Washington, D.C.)
- General Hospital Psychiatry
- The Canadian Journal of Clinical Pharmacology = Journal Canadien De Pharmacologie Clinique
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses
- Cancer
- Addictive Behaviors
- Academic Radiology
- The Journal of Laryngology and Otology
- Psychological Medicine
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- The Journal of Bone and Joint Surgery. American Volume
- MLO: Medical Laboratory Observer
- The European Journal of Neuroscience
- Studies in Health Technology and Informatics
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- Journal of Applied Microbiology
- Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
- Epilepsia
- Schizophrenia Research
- Nutrition and Cancer
- British Journal of Cancer
- Applied and Environmental Microbiology
- The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
- Comparative Medicine
- Medical Teacher
- Molecular BioSystems
- Molecular Biology of the Cell
- International Journal of Circumpolar Health
- Journal of Cancer Education : the Official Journal of the American Association for Cancer Education
- Journal of Alzheimer's Disease : JAD
- Medical Teacher
- Journal of Neurosurgery. Pediatrics
- American Heart Journal
- Autism Research : Official Journal of the International Society for Autism Research
- The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
- Substance Use & Misuse
- Journal of Affective Disorders
- Pediatric Radiology
- Nutrition Research (New York, N.Y.)
- Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine
- Molecular Biology of the Cell
- International MS Journal / MS Forum
- Multiple Sclerosis (Houndmills, Basingstoke, England)
- The New Zealand Medical Journal
- Evolution; International Journal of Organic Evolution
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- Plant Physiology
- Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine
- Cancer Research
- BMC Research Notes
- The Journal of Bone and Joint Surgery. British Volume
- Lancet
- Lancet
- Journal of Medicinal Chemistry
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- The New Zealand Medical Journal
- Frontiers in Neuroscience
- BMC Complementary and Alternative Medicine
- BMC Psychiatry
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
- Nursing Management
- BMC Cancer
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- Clinical Practice and Epidemiology in Mental Health : CP & EMH
- Ecological Applications : a Publication of the Ecological Society of America
- International Maritime Health
- American Journal of Physiology. Endocrinology and Metabolism
- Journal of Psychiatric Research
- FEMS Microbiology Ecology
- Blood
- Bioconjugate Chemistry
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Clinical Nurse Specialist CNS
- Nano Letters
- Pain Practice : the Official Journal of World Institute of Pain
- PloS One
- Social Psychiatry and Psychiatric Epidemiology
- The European Journal of Neuroscience
- Drug Metabolism and Disposition: the Biological Fate of Chemicals
- Journal of Affective Disorders
- British Journal of Haematology
- BMC Geriatrics
- FEMS Microbiology Ecology
- American Journal of Epidemiology
- Endocrine Pathology
- Endocrine, Metabolic & Immune Disorders Drug Targets
- Clinical Nurse Specialist CNS
- American Journal of Preventive Medicine
- Clinical and Experimental Gastroenterology
- Chronic Diseases and Injuries in Canada
- Psychological Medicine
- Drug Safety : an International Journal of Medical Toxicology and Drug Experience
- Journal of Affective Disorders
- American Journal of Physiology. Cell Physiology
- Irish Veterinary Journal
- ACS Nano
- Journal of the Mechanical Behavior of Biomedical Materials
- Endocrine, Metabolic & Immune Disorders Drug Targets
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- Journal of Speech, Language, and Hearing Research : JSLHR
- Conservation Biology : the Journal of the Society for Conservation Biology
- Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine
- International Journal of Behavioral Medicine
- CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne
- Molecular Medicine (Cambridge, Mass.)
- Brain Research
- Genes, Chromosomes & Cancer
- Genes, Chromosomes & Cancer
- Langmuir : the ACS Journal of Surfaces and Colloids
- Medical Hypotheses
- The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
- Psycho-oncology
- The Journal of Biological Chemistry
- Drug Metabolism and Disposition: the Biological Fate of Chemicals
- Proceedings. Biological Sciences / The Royal Society
- Bone Marrow Transplantation
- The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
- American Journal of Speech-language Pathology / American Speech-Language-Hearing Association
- Breast Cancer Research and Treatment
- European Psychiatry : the Journal of the Association of European Psychiatrists
- Annals of Biomedical Engineering
- The Journal of Biological Chemistry
- Oncology
- European Journal of Applied Physiology
- Food & Function
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- Headache
- International Journal of Surgery Case Reports
- Head and Neck Pathology
- Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
- The Annals of Thoracic Surgery
- Journal of Child and Adolescent Psychopharmacology
- CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne
- American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists
- Trends in Endocrinology and Metabolism: TEM
- Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
- Nursing
- The American Journal of Nursing
- Epilepsia
- Clinical Neuropharmacology
- Occupational and Environmental Medicine
- Journal of Psychiatric Research
- Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology
- International Journal of Surgery Case Reports
- Bioorganic & Medicinal Chemistry Letters
- Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists
- Psychiatric Services (Washington, D.C.)
- Journal of Cancer Education : the Official Journal of the American Association for Cancer Education
- The Journal of Biological Chemistry
- Multiple Sclerosis (Houndmills, Basingstoke, England)
- Gastrointestinal Endoscopy Clinics of North America
- Evidence-based Mental Health
- Neuropharmacology
- Social Psychiatry and Psychiatric Epidemiology
- American Journal of Clinical Oncology
- Addictive Behaviors
Automatic Translation
This translation into Hebrew was automatically generated.
English Version | Other Languages
Articles by D. Patten in JoVE
מדידות אלקטרו וניתוח Nociception אצל תינוקות אדם
L. Fabrizi*1, A. Worley*2, D. Patten1, S. Holdridge1, L. Cornelissen1, J. Meek3, S. Boyd2, R. Slater1,4
1Neuroscience, Physiology and Pharmacology, University College London, 2Department of Clinical Neurophysiology, Great Ormond Street Hospital, 3Elizabeth Garrett Anderson Obstetric Hospital, University College Hospital, 4Nuffield Department of Anaesthetics, University of Oxford
הערכה וטיפול של כאב אצל תינוקות קשה בגלל שתינוקות לא יכולים לדווח מילולית הניסיון שלהם. בסרט זה אנו מתארים שיטות אלקטרו כמותיים וטכניקות ניתוח זה יכול לשמש כדי למדוד את התגובה לאירועים הרעילים ממערכת העצבים התינוק.
Other articles by D. Patten on PubMed
A Cross-cultural Comparison of Anatomy Learning: Learning Styles and Strategies
Anatomical Sciences Education. Mar-Apr, 2009 | Pubmed ID: 19347948
Cultural influences on anatomy teaching and learning have been investigated by application of a questionnaire to medical students in British and Chinese Medical Schools. Results from the responses from students of the two countries were analyzed. Both groups found it easier to understand anatomy in a clinical context, and in both countries, student learning was driven by assessment. Curriculum design differences may have contributed to the British view wherein students were less likely to feel time pressure and enjoyed studying anatomy more than their Chinese counterparts. Different teaching approaches resulted in British students being more likely to recite definitions to learn, and the Chinese students found learning from cross-sectional images easy. Cultural differences may account for the observation that British students were more inclined to ask questions in class, and the preference of Chinese students to study in small groups. The findings give evidence to show how 'cultures of learning' influence students' approaches and indicate the importance of cultural influences as factors amongst international and home learner groups.
Elevated Levels of Soluble P-selectin in Mice Alter Blood-brain Barrier Function, Exacerbate Stroke, and Promote Atherosclerosis
Blood. Jun, 2009 | Pubmed ID: 19349621
Cerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of increased levels of sP-selectin on blood-brain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-sel(DeltaCT/DeltaCT) mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-sel(DeltaCT/DeltaCT) mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres; (2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE(-/-) genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications.
Feasibility of a Telephone-based Intervention for Support Persons to Help Smokers Quit: a Pilot Study
Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Apr, 2009 | Pubmed ID: 19357315
Nonsmokers have a potentially supportive role in tobacco cessation efforts. The present study examined the feasibility, acceptability, and potential efficacy of a telephone-based intervention for nonsmoking support persons.
Virtual Histology Intravascular Ultrasound Assessing the Risk of Cardiac Allograft Vasculopathy
Journal of the American College of Cardiology. Apr, 2009 | Pubmed ID: 19358942
PKCgamma-induced Trafficking of AMPA Receptors in Embryonic Zebrafish Depends on NSF and PICK1
Proceedings of the National Academy of Sciences of the United States of America. Apr, 2009 | Pubmed ID: 19366675
The trafficking of AMPA receptors (Rs) to and from synaptic membranes is a key component underlying synaptic plasticity mechanisms such as long-term potentiation (LTP) and long-term depression (LTD), and is likely important for synaptic development in embryonic organisms. However, some of the key biochemical components required for receptor trafficking in embryos are still unknown. Here, we report that in embryonic zebrafish, the activation of PKCgamma by phorbol 12-myristate 13-acetate, strongly potentiates the amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs) via a N-ethylmaleimide-sensitive fusion (NSF) and protein interacting with C-kinase-1 (PICK1)-dependent process. We found that the mEPSC potentiation is DAG- and Ca(2+)-dependent, and occurs on application of active PKCgamma. Peptides that prevent the association of NSF and PICK1 with the GluR2 subunit, and the actin-polymerization blocker, latrunculin B, prevented the increase in mEPSC amplitude. Also, application of tetanus toxin (TeTx), which cleaves SNARE proteins, also blocked the increase in mEPSC amplitude. Last, application of a 5 mM K(+) medium led to an enhancement in mEPSC amplitude that was prevented by addition of the PKCgamma and NSF-blocking peptides, and the NMDA receptor blocker, 2-amino-5-phosphonovaleric acid (APV). Thus, activation of PKCgamma is necessary for the activity-dependent trafficking of AMPARs in embryonic zebrafish. This process is NMDA and SNARE-dependent and requires AMPARs to associate with both NSF and PICK1. The present data further our understanding of AMPAR trafficking, and have important implications for synaptic development and synaptic plasticity.
Disability Payments for Persons with Severe Mental Illness in Alberta, Canada
Psychiatric Services (Washington, D.C.). May, 2009 | Pubmed ID: 19411359
The authors measured the total expenditures for two key sources of social support in Alberta in 2005 for persons with severe and persistent mental illness and compared these expenditures with the total mental health expenditures.
The Utility of a Touch Preparation in the Diagnosis of Fluctuant Subcutaneous Fat Necrosis of the Newborn
Pediatric Dermatology. Mar-Apr, 2009 | Pubmed ID: 19419492
Subcutaneous fat necrosis of the newborn (SFNN) is an uncommon self-limiting panniculitis. Lesions may be fluctuant and spontaneously drain. Here we report a technique to rapidly confirm the diagnosis of SFNN when fluctuance exists via a touch preparation that demonstrates the characteristic histologic features of this condition. The material can be collected by fine needle aspirate, from draining fluctuant lesions, or if biopsy if performed.
Accumulation of Major Depressive Episodes over Time in a Prospective Study Indicates That Retrospectively Assessed Lifetime Prevalence Estimates Are Too Low
BMC Psychiatry. 2009 | Pubmed ID: 19422724
Most epidemiologic studies concerned with Major Depressive Disorder have employed cross-sectional study designs. Assessment of lifetime prevalence in such studies depends on recall of past depressive episodes. Such studies may underestimate lifetime prevalence because of incomplete recall of past episodes (recall bias). An opportunity to evaluate this issue arises with a prospective Canadian study called the National Population Health Survey (NPHS).
Parental Sex Discrimination and Intralocus Sexual Conflict
Biology Letters. Oct, 2009 | Pubmed ID: 19435832
Intralocus sexual conflict occurs when populations segregate for alleles with opposing fitness consequences in the two sexes. This form of selection is known to be capable of maintaining genetic and fitness variation in nature, the extent of which is sensitive to the underlying genetics. We present a one-locus model of a haploid maternal effect that has sexually antagonistic consequences for offspring. The evolutionary dynamics of these maternal effects are distinct from those of haploid direct effects under sexual antagonism because the relevant genes are expressed only in females. Despite this, we find the same opportunity for sexually antagonistic polymorphism at the maternal effect locus as at a direct effect locus. Thus, sexually antagonistic maternal effects may underlie some natural genetic variation. The model we present permits alternative interpretations of how the genes are expressed and how the fitness variation is assigned, which invites a theoretical comparison to models of both imprinted genes and sex allocation.
Inhibition of VEGF or TGF-{beta} Signaling Activates Endothelium and Increases Leukocyte Rolling
Arteriosclerosis, Thrombosis, and Vascular Biology. Aug, 2009 | Pubmed ID: 19461051
Motivated by the central roles that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta play in the assembly and maintenance of the vasculature, we examined the impact of systemic VEGF or TGF-beta signal inhibition on endothelial activation as detected by leukocyte-endothelial interactions.
A Randomized, Controlled Trial of Bupropion Sustained-release for Preventing Tobacco Relapse in Recovering Alcoholics
Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Jul, 2009 | Pubmed ID: 19483180
Studies examining the efficacy of tobacco dependence treatment among recovering alcoholic smokers have produced mixed findings. We set out to investigate this issue further by conducting a randomized, double-blind, placebo-controlled trial of bupropion sustained-release (SR) for smoking relapse prevention among abstinent alcoholic smokers.
Avoidance Behavior by Prairie Grouse: Implications for Development of Wind Energy
Conservation Biology : the Journal of the Society for Conservation Biology. Oct, 2009 | Pubmed ID: 19500121
New wind-energy facilities and their associated power transmission lines and roads are being constructed at a rapid pace in the Great Plains of North America. Nevertheless, little is known about the possible negative effects these anthropogenic features might have on prairie birds, one of the most threatened groups in North America. We examined radiotelemetry tracking locations of Lesser Prairie-Chickens (Tympanuchus pallidicinctus) and Greater Prairie-Chickens (T. cupido) in two locations in Oklahoma to determine whether these birds avoided or changed movement behavior near power lines and paved highways. We tracked 463 Lesser Prairie-Chickens (15,071 tracking locations) and 216 Greater Prairie-Chickens (5,750 locations) for 7 and 3 years, respectively. Individuals of both species avoided power lines by at least 100 m and Lesser Prairie-Chickens avoided one of the two highways by 100 m. Prairie-chickens crossed power lines less often than expected if birds moved randomly (p < 0.05) but did not appear to perceive highways as a movement barrier (p > 0.05). In addition, home ranges of Lesser Prairie-Chickens overlapped the power line less often than would be expected by chance placement of home ranges; this result was supported by kernel-density estimation of home ranges. It is likely that new power lines (and other tall structures such as wind turbines) will lead to avoidance of previously suitable habitat and will serve as barriers to movement. These two factors will likely increase fragmentation in an already fragmented landscape if wind energy development continues in prairie habitats.
Radioligand Binding Assays: Application of [(125)I]angiotensin II Receptor Binding
Methods in Molecular Biology (Clifton, N.J.). 2009 | Pubmed ID: 19513646
Angiotensin II (AngII) is an octapeptide hormone with a key role in blood pressure regulation. AngII increases blood pressure by stimulating G protein-coupled receptors in vascular smooth muscle. AngII receptors are therefore an important target in patients with high blood pressure. Strategies to lower high blood pressure (hypertension) include the use of drugs that compete for AngII at the angiotensin II Type 1 receptors (ATR) using ATR antagonists (e.g., irbesartan, valsartan, and losartan). This chapter will demonstrate the subtype specificity of ATR binding and we discuss some of the key experiments that are necessary in optimizing some of the parameters for GPCR screening. The latter protocols include saturation binding to determine K (d) and B (max), as well as competition/inhibition experiments to determine the IC(50) of binding. For these experiments we have used rat liver membranes which express ATR (type 1a) in relatively abundant amounts. Additionally, rat liver membrane preparations can be easily prepared in "bulk," frozen away for extended periods (up to 1 year) and used when necessary with no loss of receptor binding activity using the radiolabeled angiotensin II analogue, [(125)I][Sar(1),I le(8)]AngII.
Pilot Study of Lokomat Versus Manual-assisted Treadmill Training for Locomotor Recovery Post-stroke
Journal of Neuroengineering and Rehabilitation. 2009 | Pubmed ID: 19523207
While manually-assisted body-weight supported treadmill training (BWSTT) has revealed improved locomotor function in persons with post-stroke hemiparesis, outcomes are inconsistent and it is very labor intensive. Thus an alternate treatment approach is desirable. Objectives of this pilot study were to: 1) compare the efficacy of body-weight supported treadmill training (BWSTT) combined with the Lokomat robotic gait orthosis versus manually-assisted BWSTT for locomotor training post-stroke, and 2) assess effects of fast versus slow treadmill training speed.
Designing a Knowledge Transfer and Exchange Strategy for the Alberta Depression Initiative: Contributions of Qualitative Research with Key Stakeholders
International Journal of Mental Health Systems. 2009 | Pubmed ID: 19523226
Depressive disorders are highly prevalent and of significant societal burden. In fall 2004, the 'Alberta Depression Initiative' (ADI) research program was formed with a mission to enhance the mental health of the Alberta population. A key expectation of the ADI is that research findings will be effectively translated to appropriate research users. To help ensure this, one of the initiatives funded through the ADI focused specifically on knowledge transfer and exchange (KTE). The objectives of this project were first to examine the state of the KTE literature, and then based on this review and a set of key informant interviews, design a KTE strategy for the ADI.
Three-dimensional Modeling of HCFC-123 in the Atmosphere: Assessing Its Potential Environmental Impacts and Rationale for Continued Use
Environmental Science & Technology. May, 2009 | Pubmed ID: 19534136
HCFC-123 (C2HCl2F3) is used in large refrigeration systems and as a fire suppression agent blend. Like other hydrochlorofluorocarbons, production and consumption of HCFC-123 is limited under the Montreal Protocol on Substances that Deplete the Ozone Layer. The purpose of this study is to update the understanding of the current and projected impacts of HCFC-123 on stratospheric ozone and on climate and to discuss the potential environmental effects from continued use of this chemical for specific applications. For the first time, the Ozone Depletion Potential (ODP) of a HCFC is determined using a three-dimensional model (MOZART-3) of atmospheric physics and chemistry. All previous studies have relied on results from two-dimensional models. The derived HCFC-123 ODP of 0.0098 is smaller than previous values. Analysis of the projected uses and emissions of HCFC-123, assuming reasonable levels of projected growth and use in centrifugal chiller and fire suppressant applications, suggests an extremely small impact on the environment due to its short atmospheric lifetime, low ODP, low Global Warming Potential (GWP), and the small production and emission of its limited applications. The current contribution of HCFC-123 to stratospheric reactive chlorine is too small to be measurable.
Feasibility of an Exercise Counseling Intervention for Depressed Women Smokers
Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Aug, 2009 | Pubmed ID: 19541948
Depressive symptoms negatively impact smoking abstinence. However, few interventions have been targeted to smokers with current depression. Exercise improves mood and may benefit depressed smokers. This pilot study investigated the feasibility of an exercise intervention for depressed female smokers (Center for Epidemiological Studies Depression Scale [CES-D] score > or =16).
Major Depression and Health-related Quality of Life in Parkinson's Disease
General Hospital Psychiatry. Jul-Aug, 2009 | Pubmed ID: 19555793
Depression is a common psychiatric condition in Parkinson's disease (PD), yet the burden of depression on health-related quality of life (HRQL) has not been clearly delineated in this patient population.
Maintenance or Loss of Genetic Variation Under Sexual and Parental Antagonism at a Sex-linked Locus
Evolution; International Journal of Organic Evolution. Nov, 2009 | Pubmed ID: 19573084
An intralocus genetic conflict occurs when a locus is selected in opposing directions in different subsets of a population. Populations with two sexes have the potential to host a pair of distinct intralocus conflicts: sexual antagonism and parental antagonism. In this article, we examine the population genetic consequences of these conflicts for X-linked genes. Both conflicts are capable of maintaining genetic variation in a population, but to different degrees. For weak sexual antagonism, the X chromosome has a higher opportunity for polymorphism than the autosomes. For parental antagonism, there is a very limited opportunity for polymorphism on the X chromosome relative to autosomes or to sexual antagonism. X-linkage introduces an asymmetry in the inheritance and expression of sexually and parentally antagonistic genes that leads to a biased fixation of alleles with certain effects. We find little support for the commonly held intuition that the X chromosome should be biased toward fixing female-beneficial alleles. Contrary to this intuition, we find that the X chromosome is biased toward fixation of male-beneficial alleles for much of the range of dominance. Additionally, we find that the X chromosome is more favorable to the fixation of alleles that are beneficial when maternally derived.
Solution-phase Parallel Synthesis of Hsp90 Inhibitors
Journal of Combinatorial Chemistry. Sep-Oct, 2009 | Pubmed ID: 19583220
As part of an oncology chemistry program directed toward discovery of orally bioavailable inhibitors of the 90 kDa heat shock protein (Hsp90), several solution-phase libraries were designed and prepared. A 2 x 89 library of racemic resorcinol amides was prepared affording 131 purified compounds. After evaluation in a binding assay, followed by an AKT-Luminex cellular assay, three potent analogs had functional activity between 0.1 and 0.3 microM. Resolution by preparative chiral SFC chromatography led to (+)-15, (+)-16, and (+)-17 having functional IC(50) = 27, 43, and 190 nM, respectively. (+)-15 exhibited high clearance in human hepatocytes driven primarily by glucuronidation as confirmed by metabolite identification. A second 8 x 14 exploratory library was designed to investigate heterocyclic replacements of the resorcinol ring. The second library highlights the use of the (-)-sparteine-mediated enantioselective Pd-catalyzed alpha-arylation of N-Boc-pyrrolidine to prepare chiral 2-arylpyrrolidines in parallel.
Anatomic Relationship of the Radial Nerve to the Elbow Joint: Clinical Implications of Safe Pin Placement
Clinical Anatomy (New York, N.Y.). Sep, 2009 | Pubmed ID: 19637299
The percutaneous placement of lateral distal humeral pins risks injury to the radial nerve. We aimed to provide a reliable and safe parameter for the insertion of lateral distal humeral pins. A secondary aim of this study was to investigate the effect of pin/screw placement in the intended zone of fixation at the lateral distal humerus. We dissected 70 fresh cadaveric upper limbs and the radial nerve was identified and its course followed into the anterior compartment. The point where the radial nerve crosses humerus in mid lateral plane was identified and the distance between this point and lateral epicondyle was measured, as was the maximum trans-epicondylar distance, along with the olecranon fossa height. Statistical analysis was performed using the Pearson correlation coefficient. The average trans-epicondylar distance was measured at 62 +/- 6 mm (range 52-78 mm), and the average lateral radial nerve height was 102 +/- 10 mm (range 75-129 mm). The ratio of the lateral nerve height to the trans-epicondylar distance was an average of 1.7 +/- 0.2 (range 1.4-2.0). The Pearson correlation coefficient between the lateral nerve height and the trans-epicondylar distance was r = 0.95. A relative dimension, the trans-epicondylar distance is both reliable and easily accessible to the operating surgeon. The absolute safe zone for pin entry into the lateral distal humerus is that area lying within the caudad 70% of a line, equivalent in length to the patient's own trans-epicondylar distance, when projected proximally from the lateral epicondyle.
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. IV. Neurostimulation Therapies
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19656575
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is renewed interest in refined approaches to brain stimulation, particularly for treatment resistant major depressive disorder (MDD).
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. V. Complementary and Alternative Medicine Treatments
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19666194
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is widespread interest in complementary and alternative medicine (CAM) therapies in the treatment of major depressive disorder (MDD).
Evidence for a Novel Bisacylphosphine Oxide Photoreaction from TRIR, TREPR and DFT Studies
Physical Chemistry Chemical Physics : PCCP. Sep, 2009 | Pubmed ID: 19672536
Magnetic field effects on the photolysis of homogeneous solutions containing (2,4,6-trimethylbenzoyl)diphenylphoshine oxide, MAPO, and bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide, BAPO, were studied using time-resolved infrared spectroscopy. The two molecules display distinctly different field dependences in conflict with established photochemistry. Time-resolved EPR was employed to examine the photochemistry in detail, resulting in the detection of previously unobserved radical species when BAPO was photoexcited in alcoholic solvents. Plausible reaction mechanisms were used to suggest candidate species that may be responsible for the new EPR signals. DFT calculations were then used to evaluate the likelihood of formation of these species and to estimate their hyperfine coupling constants for comparison with the recorded spectral data. The most likely identities of the new species are a two-coordinate phosphorus radical anion for the species with an observed hyperfine coupling of 2.9 mT and a four coordinate phosphorus centred radical for the species with the large 49.8 mT coupling.
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. III. Pharmacotherapy
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19674794
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field.
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. I. Classification, Burden and Principles of Management
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19674796
Major depressive disorder (MDD) is one of the most burdensome illnesses in Canada. The purpose of this introductory section of the 2009 revised CANMAT guidelines is to provide definitions of the depressive disorders (with an emphasis on MDD), summarize Canadian data concerning their epidemiology and describe overarching principles of managing these conditions. This section on "Classification, Burden and Principles of Management" is one of 5 guideline articles in the 2009 CANMAT guidelines.
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. II. Psychotherapy Alone or in Combination with Antidepressant Medication
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19682749
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. This article, one of five in the series, reviews new studies of psychotherapy in the acute and maintenance phase of MDD, including computer-based and telephone-delivered psychotherapy.
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the Management of Major Depressive Disorder in Adults. Introduction
Journal of Affective Disorders. Oct, 2009 | Pubmed ID: 19682750
Latency to Facial Expression Change Following Noxious Stimulation in Infants is Dependent on Postmenstrual Age
Pain. Nov, 2009 | Pubmed ID: 19682794
Change in facial expression over a fixed time after a noxious stimulus is the key measure used to calculate pain scores in preterm and newborn infants. We hypothesised that the latency of facial motor responses would be longer in the youngest premature infants and that behavioural scoring methods of pain may need to take this into account. One hundred and seventy-two clinically required heel lances were performed in 95 infants from 25 to 44 weeks postmenstrual age (PMA). Sixty-four percentage of the heel lances evoked a change in facial expression. Change in facial expression was observed in infants across the whole age range from 25 weeks PMA and the latency to the facial expression response ranged from 1 to 17s. Latency to facial expression change was dependent on the infants' PMA at the time of the heel lance. Infants below 32 weeks PMA had a significantly longer latency to change in facial expression than older infants (54% increase in infants below 32 weeks; p < 0.001). Sleep state and presence of brain damage (IVH grades 1-4) did not significantly increase the latency (p > 0.05 for each variable). Intravenous morphine at the time of the heel lance significantly increased the latency to facial expression response (p < 0.001) but the analysis shows that latency is highly dependent on PMA independent of morphine administration. These findings highlight developmental changes underlying infant behaviour that are critically important if pain scores are to be correctly interpreted.
Von Willebrand Factor-cleaving Protease ADAMTS13 Reduces Ischemic Brain Injury in Experimental Stroke
Blood. Oct, 2009 | Pubmed ID: 19687510
Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platelets, is elevated in patients with acute stroke. The activity of VWF is modulated by ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) that cleaves VWF to smaller less-active forms. We recently documented that ADAMTS13 negatively regulates both thrombosis and inflammation. We report that deficiency or reduction of VWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury. In contrast, ADAMTS13 deficiency results in larger infarctions, but only in mice that have VWF. Importantly, infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Furthermore, recombinant ADAMTS13 did not enhance bleeding in a hemorrhagic stroke model. Our findings show the importance of VWF in regulating infarction and suggest that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke.
New Therapeutic Agents for Castration-refractory Prostate Cancer
Clinical Genitourinary Cancer. Aug, 2009 | Pubmed ID: 19692323
Validation of the Support Provided Measure Among Spouses of Smokers Receiving a Clinical Smoking Cessation Intervention
Psychology, Health & Medicine. Aug, 2009 | Pubmed ID: 19697254
Studies indicate a positive association between social support and smoking cessation. However, clinic-based interventions designed to increase social support have had limited success. Most studies have relied on only the smoker's perceptions of support received while few have assessed the support provider's report of support delivered. Understanding supportive interactions between support providers and recipients may assist in developing effective support interventions for cessation. The current investigation examined the perceptions of smoking-specific support provided by the spouse of a partner who smokes and was seen for a nicotine dependence consultation. Specifically, we examined spouse reported willingness to help their spouse quit, interest in learning ways to help their spouse quit, and characteristics associated with the provision of smoking-specific supportive behaviors (as assessed via the Support Provided Measure, SPM), in the 2-weeks prior to the consultation. The current investigation also examined the concurrent validity of the SPM with a validated measure of support provided to a smoker, the Partner Interaction Questionnaire (PIQ), accounting for social desirability bias and smoker readiness to change. The sample comprised 84 adult cigarette smokers seen for a clinical smoking cessation intervention and their spouses (N = 84). Results indicate that a high percentage of spouses are willing to help their partner who smokes and interested in learning way to help. As expected, spouses who were females and had never smoked had higher scores on the SPM than males or current smokers. The SPM was significantly correlated with the PIQ positive (r = 0.50, p < 0.01) and negative (r = 0.44, p <0.01) item scales overall and for spouses whose partners reported higher levels of readiness to quit smoking (r = 0.54, p < 0.01; r = 0.50, p < 0.01, respectively). Suggestions for future research are offered.
Patterns of Benzodiazepine Use in a Canadian Population Sample
Epidemiologia E Psichiatria Sociale. Jul-Sep, 2009 | Pubmed ID: 20034203
The objective of this study was to identify clinical and demographic factors that may be associated with benzodiazepine treatment, to describe the reported reasons for use of these medications and to appraise the pattern of use in relation to standard guidelines in a general population sample.
Prospective Evaluation of the Effect of Major Depression on Working Status in a Population Sample
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Dec, 2009 | Pubmed ID: 20047723
Numerous surveys have reported associations between major depressive episodes (MDEs) and occupational status, but cross-sectional studies cannot quantify the risks of employment transitions nor clarify their temporal direction. The goal of our study was to estimate the impact of MDE on subsequent employment status in a longitudinal community cohort.
Has 'lifetime Prevalence' Reached the End of Its Life? An Examination of the Concept
International Journal of Methods in Psychiatric Research. Dec, 2009 | Pubmed ID: 20052690
Many cross-sectional surveys in psychiatric epidemiology report estimates of lifetime prevalence, and the results consistently show a declining trend with age for such disorders as depression and anxiety. In a closed cohort with no mortality, lifetime prevalence should increase or remain constant with age. For mortality to account for declining lifetime prevalence, mortality rates in those with a disorder must exceed those without a disorder by a sufficient extent that more cases would be removed from the prevalence pool than are added by new cases, and this is unlikely to occur across most of the age range. We argue that the decline in lifetime prevalence with age cannot be explained by period or cohort effects or be due to a survivor effect, and are likely due to a variety of other factors, such as study design, forgetting, or reframing. Further, because lifetime prevalence is insensitive to changes in treatment effectiveness or demand for services, it is a parameter that should be dropped from the lexicon of psychiatric epidemiology.
The Relationship Between Major Depression and Marital Disruption is Bidirectional
Depression and Anxiety. 2009 | Pubmed ID: 19798680
Marital status is important to the epidemiology of psychiatric disorders. In particular, the high prevalence of major depression in individuals with separated, divorced, or widowed status has been well documented. However, the literature is divided as to whether marital disruption results in major depression and/or vise versa. We examined whether major depression influences changes of marital status, and, conversely, whether marital status influences the incidence of this disorder.
Diversity of NirK Denitrifying Genes and Transcripts in an Agricultural Soil
Applied and Environmental Microbiology. Dec, 2009 | Pubmed ID: 19801455
Environmental conditions can change dramatically over a crop season and among locations in an agricultural field and can increase denitrification and emissions of the potent greenhouse gas nitrous oxide. In a previous study, changes in the overall size of the denitrifier community in a potato crop field were relatively small and did not correlate with variations in environmental conditions or denitrification rates. However, denitrifying bacteria are taxonomically diverse, and different members of the community may respond differently to environmental changes. The objective of this research was to understand which portion of the nirK denitrifying community is active and contributes to denitrification under conditions in a potato crop field. Denaturing gradient gel electrophoresis (DGGE) of nirK genes in soil-extracted DNA showed changes in the composition of the nirK denitrifier community over the growing season and among spatial locations in the field. By contrast, the composition of the active nirK denitrifier community, as determined by DGGE analysis of nirK transcripts derived from soil-extracted mRNA, changed very little over time, although differences in the relative abundance of some specific transcripts were observed between locations. Our results indicate that the soil denitrifier populations bearing nirK genes are not all contributing to denitrification and that the denitrifying populations that are active are among the most abundant and ubiquitous nirK-bearing denitrifiers. Changes in the community composition of the total and active nirK denitrifiers were not strongly correlated with changes in environmental factors and denitrification activity.
Small Animal Models of Heart Failure: Development of Novel Therapies, Past and Present
Circulation. Heart Failure. Mar, 2009 | Pubmed ID: 19808329
Premalignant and Malignant Cells in Sputum from Lung Cancer Patients
Cancer. Dec, 2009 | Pubmed ID: 19852034
The objective of this study was to assess the frequency of premalignant and malignant cells in sputum from patients with lung cancer and to measure the dependence of these cells on cancer stage, histologic type, tumor size, and tumor location.
Population-based Service Planning for Implementation of MBCT: Linking Epidemiologic Data to Practice
Psychiatric Services (Washington, D.C.). Nov, 2009 | Pubmed ID: 19880476
The study explored population-based service planning for mindfulness-based cognitive therapy (MBCT). Evidence suggests the usefulness of MBCT in relapse prevention for individuals reporting three or more major depressive episodes.
A Longitudinal Community Study of Major Depression and Physical Activity
General Hospital Psychiatry. Nov-Dec, 2009 | Pubmed ID: 19892216
The objective of this study was to determine whether major depressive episodes (MDEs) are associated transitions between active and inactive recreational activity patterns.
Sleep Medication Use in Canadian Seniors
The Canadian Journal of Clinical Pharmacology = Journal Canadien De Pharmacologie Clinique. 2009 | Pubmed ID: 19923638
Difficulty sleeping is a common complaint by older people which leads to medication use to help attain sleep.
Exploiting the 1/f Structure of Neural Signals for the Design of Integrated Neural Amplifiers
Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2009 | Pubmed ID: 19964775
Neural amplifiers require a large time-constant high-pass filter at approximately 1Hz to reject large DC offsets while amplifying low frequency neural signals. This high pass filter is typically realized using large area capacitors and teraohm resistances which makes integration difficult. In this paper, we present a novel topology for a neural amplifier which exploits the (1/f)(n) power spectra of local field potentials (LFP). Using a high-pass filter at approximately 100Hz, we pre-filter the LFP before amplification. Post digitization, we can recover the LFP signal by building the inverse of the high pass filter in software. We built an array of neural amplifiers based on this principle and tested it on rats chronically implanted with microelectrode arrays. We found that we could recover the initial LFP signal and the power spectral information over time with correlation coefficient greater than 0.94.
Comparison of Methods to Facilitate Postoperative Bowel Function
Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. Jul-Aug, 2009 | Pubmed ID: 20552850
Improving postoperative return of bowel function after abdominal surgery is an important nursing and medical goal. One promising intervention to achieve this goal is to have patients chew gum several times per day in the early postoperative period to stimulate the cephalic-vagal reflex and bowel peristalsis. A study to determine if return of gastrointestinal function after abdominal surgery could be hastened by the simple intervention of chewing gum or sucking on hard candy three times per day is described.
Relationship Between Cytokine Gene Single Nucleotide Polymorphisms and Symptom Burden and Quality of Life in Lung Cancer Survivors
Cancer. Sep, 2010 | Pubmed ID: 20564140
Previous research has demonstrated that many lung cancer survivors report difficulties with symptom control and experience a poor quality of life (QOL). Although recent studies have suggested a relationship of single nucleotide polymorphisms (SNPs) in several cytokine genes with cancer susceptibility and prognosis, associations with symptom burden and QOL have not been examined. The current study was conducted to identify SNPs related to symptom burden and QOL outcomes in lung cancer survivors.
Failure to Report Attempts to Quit Smoking
Addictive Behaviors. Oct, 2010 | Pubmed ID: 20584571
Accurately assessing quit attempt history is important to develop population estimates of cessation and to increase our understanding of smoking trajectories. Thus, the current study investigated failure to report quit attempts as a function of length of quit attempt by time since quit attempt over the past year.
Perceptions of Lung Cancer Risk and Beliefs in Screening Accuracy of Spiral Computed Tomography Among High-risk Lung Cancer Family Members
Academic Radiology. Aug, 2010 | Pubmed ID: 20599157
Spiral computed tomography (SCT) is being evaluated as a screening tool for lung cancer. Our objective was to describe the effect of participation in SCT screening on participants' risk perceptions, worry, and expectations regarding the accuracy of the screening result.
Lemierre's and Lemierre's-like Syndromes in Association with Infectious Mononucleosis
The Journal of Laryngology and Otology. Dec, 2010 | Pubmed ID: 20602850
This study aimed to review cases of Lemierre's and Lemierre's-like syndromes in paediatric patients, to examine a possible association with Epstein-Barr virus as a predisposing factor, and to assess the impact of this virus on the severity of illness.
Major Depression and Injury Risk
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. May, 2010 | Pubmed ID: 20482958
Cross-sectional epidemiologic studies have inconsistently reported associations between injuries and depressive symptoms. The significance of these findings remains unclear. Major depressive episodes (MDEs) may increase the risk of injury and injuries may increase the risk of MDEs. Longitudinal data are needed to distinguish between these possibilities.
Corrosion-induced Fracture of a Double-modular Hip Prosthesis: a Case Report
The Journal of Bone and Joint Surgery. American Volume. Jun, 2010 | Pubmed ID: 20516330
Armed Services Blood Program Deserves Proper Credit
MLO: Medical Laboratory Observer. May, 2010 | Pubmed ID: 20521524
Protein Kinase Cgamma is a Signaling Molecule Required for the Developmental Speeding of Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate Receptor Kinetics
The European Journal of Neuroscience. May, 2010 | Pubmed ID: 20525069
A key step in the maturation of glutamate synapses is the developmental speeding of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPA-R) kinetics, which occurs via a switch in receptor subtypes. However, the molecular components required for the switch in receptors are unknown. Here, we used the zebrafish preparation to show that activation of protein kinase C (PKC)gamma is necessary for the developmental speeding of AMPA-R kinetics. Targeted knockdown of PKCgamma with an antisense morpholino oligonucleotide [PKCgamma-morpholino (PKCgamma-MO)], prevents the normal speeding up of AMPA-R kinetics in Mauthner cells. PKCgamma-MO-injected embryos are incapable of trafficking AMPA-Rs following application of phorbol 12-myristate 13-acetate or PKCgamma. PKCgamma-MO-injected embryos do not hatch or exhibit the C-start escape response. Increasing synaptic activity (33 h post-fertilization embryos) by application of an elevated K(+) medium or by application of N-methyl-D-aspartate induces rapid PKCgamma-dependent trafficking of fast AMPA-Rs to synapses. Our findings reveal that PKCgamma is a molecular link underlying the developmental speeding of AMPA-Rs in zebrafish Mauthner cells.
Recent Advances in the Study of Candidate Genes for Adolescent Idiopathic Scoliosis
Studies in Health Technology and Informatics. 2010 | Pubmed ID: 20543391
We used a microarray approach to evaluate gene expression profiles in human AIS osteoblasts, and to identify genes that are differentially expressed following estrogen exposure in non-AIS and AIS human osteoblasts. We found that more than one gene is likely responsible for AIS. Furthermore, some of these genes are estrogen-regulated, suggesting a possible role of estrogens in the etiology of scoliosis.
Feasibility of a Tobacco Cessation Intervention for Pregnant Alaska Native Women
Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Feb, 2010 | Pubmed ID: 20018946
Among Alaska Native women residing in the Yukon-Kuskokwim (Y-K) Delta region of Western Alaska, about 79% smoke cigarettes or use smokeless tobacco during pregnancy. Treatment methods developed and evaluated among Alaska Native pregnant tobacco users do not exist. This pilot study used a randomized two-group design to assess the feasibility and acceptability of a targeted cessation intervention for Alaska Native pregnant women.
Overexpression of Hns in the Plant Growth-promoting Bacterium Enterobacter Cloacae UW5 Increases Root Colonization
Journal of Applied Microbiology. Jun, 2010 | Pubmed ID: 19951377
Plant growth-promoting rhizobacteria (PGPR) introduced into soil often do not compete effectively with indigenous micro-organisms for plant colonization. The aim of this study was to identify novel genes that are important for root colonization by the PGPR Enterobacter cloacae UW5.
Cadherin Expression in Gastrointestinal Tract Endometriosis: Possible Role in Deep Tissue Invasion and Development of Malignancy
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. Jan, 2010 | Pubmed ID: 19898423
Cadherins are cell surface proteins crucial for cell adhesion and tissue integrity. The mechanism of deep tissue invasion in gastrointestinal endometriosis is unknown and may be related to the altered expression of these cell surface proteins. The goal of this study was to evaluate the expression of N-cadherin, E-cadherin, and beta-catenin in peritoneal endometriotic implants, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis. Cases of peritoneal endometriosis, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis were identified from our pathology database. Immunohistochemistry was performed using antibodies against N-cadherin, E-cadherin, and beta-catenin on representative tissue sections. Cases of normal proliferative and secretory endometrium and adenomyosis were included in the study for comparison. The intensity and extent of staining for each marker was scored semiquantitatively. Appropriate positive and negative controls were used. A total of 38 cases (peritoneal endometriosis (n=14), gastrointestinal endometriosis (n=21: 11 colon, 8 appendix, 2 small bowel), and 3 cases of endometrioid carcinoma arising in colonic endometriosis (n=3)) were included in the study. Compared with normal proliferative endometrium, N-cadherin expression was decreased in intensity and extent in secretory endometrium. Peritoneal and gastrointestinal endometriosis also showed markedly decreased expression of N-cadherin compared with proliferative endometrium. All three cases of carcinoma arising in colonic endometriosis showed a total loss of N-cadherin in the tumor, but preserved E-cadherin and beta-catenin expression. In these cases, areas of benign endometriotic glands near the tumor showed weak and focal N-cadherin expression that was gradually lost. Moderate-to-strong membranous staining for beta-catenin expression and variable intensity of E-cadherin expression was seen diffusely in normal endometrium and all study cases. These results strongly suggest that alterations of N-cadherin expression in gastrointestinal endometriosis may have an important role in the mechanism that underlies deep tissue invasion, and possibly also in the development of malignancy.
Health Status and Health-related Behaviors in Epilepsy Compared to Other Chronic Conditions--a National Population-based Study
Epilepsia. May, 2010 | Pubmed ID: 20067511
The negative impact of epilepsy is disproportionate to its prevalence. Our objectives were to determine if health-related behaviors (HRBs) and health status differ between patients with epilepsy, migraine, or diabetes.
Prevalence of Cardiovascular Risk Factors and Disease in People with Schizophrenia: a Population-based Study
Schizophrenia Research. Mar, 2010 | Pubmed ID: 20080392
To evaluate the prevalence of cardiovascular risk factors (CV-RF) and disease (CV-D) in people with schizophrenia.
A Phase II Trial of a Soy Beverage for Subjects Without Clinical Disease with Rising Prostate-specific Antigen After Radical Radiation for Prostate Cancer
Nutrition and Cancer. 2010 | Pubmed ID: 20099194
Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.
P53 Mutation, Deprivation and Poor Prognosis in Primary Breast Cancer
British Journal of Cancer. Feb, 2010 | Pubmed ID: 20104224
The deprivation gap for breast cancer survival remains unexplained by stage at presentation, treatment, or co-morbidities. We hypothesised that p53 mutation might contribute to the impaired outcome observed in patients from deprived communities.
Changes in Denitrifier Abundance, Denitrification Gene MRNA Levels, Nitrous Oxide Emissions, and Denitrification in Anoxic Soil Microcosms Amended with Glucose and Plant Residues
Applied and Environmental Microbiology. Apr, 2010 | Pubmed ID: 20154105
In agricultural cropping systems, crop residues are sources of organic carbon (C), an important factor influencing denitrification. The effects of red clover, soybean, and barley plant residues and of glucose on denitrifier abundance, denitrification gene mRNA levels, nitrous oxide (N(2)O) emissions, and denitrification rates were quantified in anoxic soil microcosms for 72 h. nosZ gene abundances and mRNA levels significantly increased in response to all organic carbon treatments over time. In contrast, the abundance and mRNA levels of Pseudomonas mandelii and closely related species (nirS(P)) increased only in glucose-amended soil: the nirS(P) guild abundance increased 5-fold over the 72-h incubation period (P < 0.001), while the mRNA level significantly increased more than 15-fold at 12 h (P < 0.001) and then subsequently decreased. The nosZ gene abundance was greater in plant residue-amended soil than in glucose-amended soil. Although plant residue carbon-to-nitrogen (C:N) ratios varied from 15:1 to 30:1, nosZ gene and mRNA levels were not significantly different among plant residue treatments, with an average of 3.5 x 10(7) gene copies and 6.9 x 10(7) transcripts g(-1) dry soil. Cumulative N(2)O emissions and denitrification rates increased over 72 h in both glucose- and plant-tissue-C-treated soil. The nirS(P) and nosZ communities responded differently to glucose and plant residue amendments. However, the targeted denitrifier communities responded similarly to the different plant residues under the conditions tested despite changes in the quality of organic C and different C:N ratios.
Impaired Voluntary Neuromuscular Activation Limits Muscle Power in Mobility-limited Older Adults
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. May, 2010 | Pubmed ID: 20156882
Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activation, may explain differences in leg extension torque and power between healthy middle-aged, healthy older, and mobility-limited older adults.
Perturbations in Cytokine Gene Expression After Inoculation of C57BL/6 Mice with Pasteurella Pneumotropica
Comparative Medicine. Feb, 2010 | Pubmed ID: 20158944
Pasteurella pneumotropica can cause inflammation and abscess formation in a variety of tissues. Most commonly, P. pneumotropica produces clinical disease in immunodeficient mice or those concurrently infected with other pathogens. Because clinical disease is infrequent in immunocompetent mice harboring P. pneumotropica, some scientists consider it an opportunistic pathogen with little clinical relevance to biomedical research. However, other infectious agents, including mouse parvoviruses, mouse rotavirus, and Helicobacter spp. alter physiologic or biologic responses without causing clinical signs of illness. We investigated the potential for P. pneumotropica to modulate the transcription of cytokine genes in immunocompetent mice. In C57BL/6 mice inoculated oronasally with a minimal colonizing dose of P. pneumotropica, modest but statistically significant elevations of IL1beta, TNFalpha, CCL3, CXCL1, and CXCL2 mRNA were detected in mandibular and superficial cervical lymph nodes at 7 d after inoculation, and upregulation of IL1beta mRNA was detected 28 d after inoculation. These perturbations were not present in C57/BL6 mice inoculated with heat killed-P. pneumotropica or the related bacterium Actinobacillus muris. Nasal mucosal cytokine transcription did not vary significantly in C57BL/6 mice given a high dose of P. pneumotropica. These data indicate that slight and transient experimental perturbations are possible in immunocompetent mice colonized with P. pneumotropica. Knowing the full health status of experimental mice is paramount to avoid unwanted experimental variables, especially when using exquisitely sensitive testing methodologies such as those for quantification of gene expression.
Student Attitudes to Peer Physical Examination: a Qualitative Study of Changes in Expressed Willingness to Participate
Medical Teacher. 2010 | Pubmed ID: 20163215
A number of studies have explored student attitudes to examining each other (peer physical examination: PPE). Differences have emerged in whether students prefer to be examined by friends or strangers. Changes have been reported in how students feel about PPE if asked before or after the PPE programme commences. RESEARCH INTENTION: Since a Grounded Theory paradigm was employed, there was no formal research hypothesis: the research intention was to explore factors which might underlie changes in student willingness to undertake PPE following familiarity with the process.
Probing Native Lignin Macromolecular Configuration in Arabidopsis Thaliana in Specific Cell Wall Types: Further Insights into Limited Substrate Degeneracy and Assembly of the Lignins of Ref8, Fah 1-2 and C4H::F5H Lines
Molecular BioSystems. Mar, 2010 | Pubmed ID: 20174679
The interest in renewable, plant-derived, bioenergy/biofuels has resulted in a renaissance of plant cell-wall/lignin research. Herein, effects of modulating lignin monomeric compositions in a single plant species, Arabidopsis, are described. The earliest stage of putative "AcBr/Klason lignin" deposition was apparently unaffected by modulating p-coumarate 3-hydroxylase or ferulate 5-hydroxylase activities. This finding helps account for the inability of many other studies to fully suppress the reported putative levels of lignin deposition through monolignol biosynthesis manipulation, and also underscores limitations in frequently used lignin analytical protocols. The overall putative lignin content was greatly reduced (circa 62%) in a plant line harboring an H-(p-hydroxyphenyl) enriched lignin phenotype. This slightly increased H-monomer deposition level apparently occurred in cell-wall domains normally harboring guaiacyl (G) and/or syringyl (S) lignin moieties. For G- and S-enriched lignin phenotypes, the overall lignification process appeared analogous to wild type, with only xylem fiber and interfascicular fiber cells forming the S-enriched lignins. Laser microscope dissection of vascular bundles and interfascicular fibers, followed by pyrolysis GC/MS, supported these findings. Some cell types, presumably metaxylem and possibly protoxylem, also afforded small amounts of benzodioxane (sub)structures due to limited substrate degeneracy (i.e. utilizing 5-hydroxyconiferyl alcohol rather than sinapyl alcohol). For all plant lines studied, the 8-O-4' inter-unit frequency of cleavable H, G and/or S monomers was essentially invariant of monomeric composition for a given (putative) lignin content. These data again underscore the need for determination of lignin primary structures and identification of all proteins/enzymes involved in control of lignin polymer assembly/macromolecular configuration.
Deficiency of the Transcriptional Regulator P8 Results in Increased Autophagy and Apoptosis, and Causes Impaired Heart Function
Molecular Biology of the Cell. Apr, 2010 | Pubmed ID: 20181828
Autophagy is a cytoprotective pathway used to degrade and recycle cytoplasmic content. Dysfunctional autophagy has been linked to both cancer and cardiomyopathies. Here, we show a role for the transcriptional regulator p8 in autophagy. p8 RNA interference (RNAi) increases basal autophagy markers in primary cardiomyocytes, in H9C2 and U2OS cells, and decreases cellular viability after autophagy induction. This autophagy is associated with caspase activation and is blocked by atg5 silencing and by pharmacological inhibitors. FoxO3 transcription factor was reported to activate autophagy by enhancing the expression of autophagy-related genes. P8 expression represses FoxO3 transcriptional activity, and p8 knockdown affects FoxO3 nuclear localization. Thus, p8 RNAi increases FoxO3 association with bnip3 promoter, a known proautophagic FoxO3 target, resulting in higher bnip3 RNA and protein levels. Accordingly, bnip3 knockdown restores cell viability and blocks apoptosis of p8-deficient cells. In vivo, p8 -/- mice have higher autophagy and express higher cardiac bnip3 levels. These mice develop left ventricular wall thinning and chamber dilation, with consequent impaired cardiac function. Our studies provide evidence of a p8-dependent mechanism regulating autophagy by acting as FoxO3 corepressor, which may be relevant for diseases associated with dysregulated autophagy, as cardiovascular pathologies and cancer.
Prevalence and Correlates of Tobacco Use Among Middle and High School Students in Western Alaska
International Journal of Circumpolar Health. Apr, 2010 | Pubmed ID: 20380809
Tobacco use is the leading cause of preventable death in the United States and contributes to increased incidence, morbidity and mortality from cancer, heart disease, stroke, complications of pregnancy and respiratory illness. Tobacco use rates are highest among American Indians and Alaska Natives. This study examined the prevalence and correlates of tobacco use among youth residing in rural western Alaska.
Development and Pilot Evaluation of a Cancer-focused Summer Research Education Program for [corrected] Navajo Undergraduate Students
Journal of Cancer Education : the Official Journal of the American Association for Cancer Education. Dec, 2010 | Pubmed ID: 20411446
This paper describes the development and pilot testing of a 10-week cancer research education program for Navajo undergraduate students. The program was piloted at Diné College with 22 undergraduates (7 men, 15 women) in 2007 and 2008. Students completed a pre-post program survey assessing attitudes, opinions, and knowledge about research and about cancer. The program was found to be culturally acceptable and resulted in statistically significant changes in some of the attitudes and opinions about research and cancer. Combining all 13 knowledge items, there was a significant (p = 0.002) change in the mean total correct percent from baseline [70.3 (SD = 15.9)] to post-program [82.1 (SD = 13.1)]. The curriculum was adapted for a new cancer prevention and control course now offered at Diné College, enhancing sustainability. Ultimately, these efforts may serve to build capacity in communities by developing a cadre of future Native American scientists to develop and implement cancer research.
Reactive Oxygen Species: Stuck in the Middle of Neurodegeneration
Journal of Alzheimer's Disease : JAD. 2010 | Pubmed ID: 20421690
Neuronal cell loss associated with neurodegeneration has recently been linked to mitochondrial dysfunction. Electron transport chain defects and reactive oxygen species (ROS) production are emerging as important players in the etiology of neurodegenerative diseases. Proper management of ROS and disposal of damaged cellular components are vital to the survival and function of neurons. Proteins involved in these pathways are often mutated in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In this review, we will discuss the roles of ROS in normal physiology, how changes in ROS production affect neuronal survival in neurodegenerative diseases, and the recent advances in mitochondrial antioxidants as potential therapeutics.
The Impact of Wearing Scrubs on Contextual Learning
Medical Teacher. 2010 | Pubmed ID: 20423256
Godden and Baddeley ( 1975 ) suggested strong contextual influence on recall, suggesting learning in an educational context might not transfer well to practice.
Neurogenic Stunned Myocardium After Acute Hydrocephalus
Journal of Neurosurgery. Pediatrics. May, 2010 | Pubmed ID: 20433252
Neurogenic stunned myocardium (NSM) is a syndrome of cardiac stunning after a neurological insult. It is commonly observed after aneurysmal subarachnoid hemorrhage but is increasingly being reported after other neurological events. The underlying mechanism of NSM is believed to be a hypothalamic-mediated sympathetic surge causing weakened cardiac contractility and even direct cardiac myocyte damage. The authors report 2 cases of NSM in pediatric patients after acute hydrocephalus. Both patients experienced severe cardiac dysfunction in the acute phase but ultimately had a good neurological outcome and a full cardiac recovery. The identification, treatment, and outcome in 2 rare pediatric cases of NSM are discussed, and the history of the brain-cardiac connection is reviewed.
Causes of Death and Rehospitalization in Patients Hospitalized with Worsening Heart Failure and Reduced Left Ventricular Ejection Fraction: Results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) Program
American Heart Journal. May, 2010 | Pubmed ID: 20435194
The postdischarge rehospitalization and death rates are high in patients with acute heart failure (HF) syndromes despite optimization of standard therapy for chronic HF. To the best of our knowledge, there has been no systematic analysis of the causes of death and rehospitalization in this patient population.
Sensory Features and Repetitive Behaviors in Children with Autism and Developmental Delays
Autism Research : Official Journal of the International Society for Autism Research. Apr, 2010 | Pubmed ID: 20437603
This study combined parent and observational measures to examine the association between aberrant sensory features and restricted, repetitive behaviors in children with autism (N=67) and those with developmental delays (N=42). Confirmatory factor analysis was used to empirically validate three sensory constructs of interest: hyperresponsiveness, hyporesponsiveness, and sensory seeking. Examining the association between the three derived sensory factor scores and scores on the Repetitive Behavior Scales--Revised revealed the co-occurrence of these behaviors in both clinical groups. Specifically, high levels of hyperresponsive behaviors predicted high levels of repetitive behaviors, and the relationship between these variables remained the same controlling for mental age. We primarily found non-significant associations between hyporesponsiveness or sensory seeking and repetitive behaviors, with the exception that sensory seeking was associated with ritualistic/sameness behaviors. These findings suggest that shared neurobiological mechanisms may underlie hyperresponsive sensory symptoms and repetitive behaviors and have implications for diagnostic classification as well as intervention.
Prevalence of Mental Disorders in a Canadian Household Population with Dementia
The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. Mar, 2010 | Pubmed ID: 20437928
Medical and mental health comorbidity in Alzheimer's disease and other dementias presents difficult challenges for health service delivery. However, existing studies have been conducted in clinical samples and may not be informative for planning community services. The Canadian Community Health Survey (CCHS) provides an opportunity to characterize associations between dementias and mental and physical comorbidity in a household population aged 55 and over.
The Association of Alcohol Consumption with Tobacco Use in Black and White College Students
Substance Use & Misuse. Jun, 2010 | Pubmed ID: 20441460
This study explored the association of alcohol and tobacco use among college students. A survey was administered in 2004 to 2,189 Black and White students from the southeastern United States. The prevalence of alcohol and tobacco use, tobacco use characteristics according to level of alcohol consumed, and percentage of students using tobacco according to type of alcoholic beverages consumed were evaluated. The interaction of race and gender with alcohol and tobacco use was explored. Our findings extend prior investigations that have found alcohol use associated with smoking and suggest attention be paid to the relation of alcohol to other forms of tobacco. Racial and gender differences are highlighted. This study was funded by Mayo Clinic. The study's limitations were noted.
The Incidence of Major Depression in Canada: the National Population Health Survey
Journal of Affective Disorders. Jun, 2010 | Pubmed ID: 19720400
To estimate the cumulative incidence of major depressive episode (MDE) over 6 years and the associations between demographic and socioeconomic variables and MDE in a sample of the Canadian national population.
Ultrasonographic Detection of Intracranial Melanocytosis in an Infant
Pediatric Radiology. Feb, 2010 | Pubmed ID: 19763554
An infant who had an extensive cutaneous melanotic nevus with satellite lesions had cranial US for an unrelated problem. Small spherical echogenic foci in the cerebral and cerebellar parenchyma were identified. Subsequent MRI confirmed these as characteristic of melanotic deposits, thereby identifying this infant as having neurocutaneous melanosis.
Butyrylated Starch Increases Large Bowel Butyrate Levels and Lowers Colonic Smooth Muscle Contractility in Rats
Nutrition Research (New York, N.Y.). Jun, 2010 | Pubmed ID: 20650351
The short-chain fatty acids acetate, propionate, and butyrate are produced by colonic bacterial fermentation of carbohydrates. Butyrate is important in the regulation of the colonocyte cell cycle and gut motility and may also reduce the risk of large bowel cancer. We have shown that dietary butyrylated starch can deliver butyrate to the large bowel in a sustained manner. We hypothesized that ingestion of butyrylated starch increases large bowel butyrate levels and decreases colonic contractility. Groups of male Sprague-Dawley rats (n = 8) were fed AIN-93G-based diet containing a highly digestible low-amylose maize starch (LAMS) control or 5% or 10% butyrylated LAMS (LAMSB) for 10 days. We found that cecal but not colonic tissue weight as well as cecal and distal colonic digesta weights and fecal output were higher in LAMSB fed rats. Butyrylated LAMS lowered digesta pH throughout the large bowel. Cecal, proximal, and distal colonic butyrate pools and portal venous butyrate concentrations were higher in rats fed LAMSB. Electrically stimulated and receptor-dependent carbachol and prostaglandin E(2)-induced isotonic contractions were lower in isolated intact sections of proximal colon (P < .05) but not the terminal ileum after 10% LAMSB ingestion. These results demonstrated that elevation of butyrate levels in the large bowel of the rat correlated with reduction of contractile activity of the colonic musculature, which may assist in the reabsorption of water and minerals.
Workplace Characteristics, Depression, and Health-related Presenteeism in a General Population Sample
Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. Aug, 2010 | Pubmed ID: 20657301
To investigate the relationships between workplace psychosocial factors, work/family conflicts, depression, and health-related presenteeism in a sample of employees who were randomly selected from the communities.
Hypoxia-inducible Factor-1 Activation in Nonhypoxic Conditions: the Essential Role of Mitochondrial-derived Reactive Oxygen Species
Molecular Biology of the Cell. Sep, 2010 | Pubmed ID: 20660157
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Different nonhypoxic stimuli, including hormones and growth factors, are also important HIF-1 activators in the vasculature. Angiotensin II (Ang II), the main effecter hormone in the renin-angiotensin system, is a potent HIF-1 activator in vascular smooth muscle cells (VSMCs). HIF-1 activation by Ang II involves intricate mechanisms of HIF-1α transcription, translation, and protein stabilization. Additionally, the generation of reactive oxygen species (ROS) is essential for HIF-1 activation during Ang II treatment. However, the role of the different VSMC ROS generators in HIF-1 activation by Ang II remains unclear. This work aims at elucidating this question. Surprisingly, repression of NADPH oxidase-generated ROS, using Vas2870, a specific inhibitor or a p22(phox) siRNA had no significant effect on HIF-1 accumulation by Ang II. In contrast, repression of mitochondrial-generated ROS, by complex III inhibition, by Rieske Fe-S protein siRNA, or by the mitochondrial-targeted antioxidant SkQ1, strikingly blocked HIF-1 accumulation. Furthermore, inhibition of mitochondrial-generated ROS abolished HIF-1α protein stability, HIF-1-dependent transcription and VSMC migration by Ang II. A large number of studies implicate NADPH oxidase-generated ROS in Ang II-mediated signaling pathways in VSMCs. However, our work points to mitochondrial-generated ROS as essential intermediates for HIF-1 activation in nonhypoxic conditions.
Diagnosing Depression in MS in the Face of Overlapping Symptoms
International MS Journal / MS Forum. Jan, 2010 | Pubmed ID: 20663414
Depression is an important problem in multiple sclerosis (MS), but the diagnosis is challenging since symptoms of depression overlap with those of MS. In the past, the main strategy has been to remove physical symptoms from scales assessing depressive symptoms in MS, but these attempts have not been successful. Depression and overlapping MS symptoms may actually share pathophysiological mechanisms, so the strategy of attempting to exclude such symptoms may be fundamentally flawed. Current diagnostic criteria provide a pragmatic solution, but it may be possible to develop improved definitions.
Challenges in Screening for Depression in Multiple Sclerosis
Multiple Sclerosis (Houndmills, Basingstoke, England). Nov, 2010 | Pubmed ID: 20685765
Screening has frequently been proposed as a strategy for detection of depression in multiple sclerosis (MS). In a recent study, we found a minimal impact of screening, even when this was coupled with rapidly responsive and evidence-based depression care.
Fitness Variation Due to Sexual Antagonism and Linkage Disequilibrium
Evolution; International Journal of Organic Evolution. Dec, 2010 | Pubmed ID: 20722728
Extensive fitness variation for sexually antagonistic characters has been detected in nature. However, current population genetic theory suggests that sexual antagonism is unlikely to play a major role in the maintenance of variation. We present a two-locus model of sexual antagonism that is capable of explaining greater fitness variance at equilibrium than previous single-locus models. The second genetic locus provides additional fitness variance in two complementary ways. First, linked loci can maintain gene variants that are lost in single-locus models of evolution, expanding the opportunity for polymorphism. Second, linkage disequilibrium results between any two sexually antagonistic genes, producing an excess of high- and low-fitness haplotypes. Our results uncover a unique contribution of conflicting selection pressures to the maintenance of variation, which simpler models that neglect genetic architecture overlook.
Frequency of Antidepressant Use in Relation to Recent and Past Major Depressive Episodes
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Aug, 2010 | Pubmed ID: 20723281
There has been a trend toward increasing antidepressant (AD) use in recent decades. We used data from the National Population Health Survey (NPHS) to determine whether this trend is continuing and to provide updated estimates of the frequency of use.
Antisense Down-regulation of 4CL Expression Alters Lignification, Tree Growth, and Saccharification Potential of Field-grown Poplar
Plant Physiology. Oct, 2010 | Pubmed ID: 20729393
Transgenic down-regulation of the Pt4CL1 gene family encoding 4-coumarate:coenzyme A ligase (4CL) has been reported as a means for reducing lignin content in cell walls and increasing overall growth rates, thereby improving feedstock quality for paper and bioethanol production. Using hybrid poplar (Populus tremula × Populus alba), we applied this strategy and examined field-grown transformants for both effects on wood biochemistry and tree productivity. The reductions in lignin contents obtained correlated well with 4CL RNA expression, with a sharp decrease in lignin amount being observed for RNA expression below approximately 50% of the nontransgenic control. Relatively small lignin reductions of approximately 10% were associated with reduced productivity, decreased wood syringyl/guaiacyl lignin monomer ratios, and a small increase in the level of incorporation of H-monomers (p-hydroxyphenyl) into cell walls. Transgenic events with less than approximately 50% 4CL RNA expression were characterized by patches of reddish-brown discolored wood that had approximately twice the extractive content of controls (largely complex polyphenolics). There was no evidence that substantially reduced lignin contents increased growth rates or saccharification potential. Our results suggest that the capacity for lignin reduction is limited; below a threshold, large changes in wood chemistry and plant metabolism were observed that adversely affected productivity and potential ethanol yield. They also underline the importance of field studies to obtain physiologically meaningful results and to support technology development with transgenic trees.
Integrated Smoking Cessation and Binge Drinking Intervention for Young Adults: a Pilot Investigation
Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. Dec, 2010 | Pubmed ID: 20730517
Alcohol consumption is strongly associated with cigarette smoking in young adults.
Interaction with Vascular Endothelium Enhances Survival in Primary Chronic Lymphocytic Leukemia Cells Via NF-kappaB Activation and De Novo Gene Transcription
Cancer Research. Oct, 2010 | Pubmed ID: 20736369
Chronic lymphocytic leukemia (CLL) cells rapidly undergo apoptosis in vitro, suggesting that the in vivo microenvironment provides crucial antiapoptotic signals. Overexpression of the antiapoptotic proteins Bcl-2 and Mcl-1 is a hallmark of CLL, and their expression is further enhanced in the lymphoid tissues. However, the high levels of Mcl-1 found in peripheral blood samples, coupled with its short half-life, led us to hypothesize that it must be actively maintained in the peripheral circulation. Coculture of CLL cells with human vascular endothelial cells significantly enhanced tumor cell survival, an effect that was not observed with normal B cells. This was associated with elevated levels of the antiapoptotic proteins Bcl-2, Mcl-1, and Bcl-X(L) and marked increased expression of CD38 and CD49d, both of which are associated with clinically aggressive disease. Because CD38, CD49d, and some Bcl-2 family genes are transcriptional targets for NF-κB, we assessed NF-κB activation following coculture with endothelial cells. DNA binding of the NF-κB subunit Rel A was significantly increased and strongly correlated with changes in transcription of CD38, CD49d, BCL2, MCL1, and BCLXL, effects that were reversed by a peptide inhibitor of Rel A. These effects were not observed following coculture with nonendothelial cell lines. Therefore, CLL cells receive specific survival signals following interaction with endothelial cells mediated through the activation of NF-κB and the induction of downstream target genes. This type of interaction in the peripheral vasculature may explain the constitutive NF-κB activation and the overexpression of Bcl-2 family proteins commonly seen in this disease.
Problems Encountered with the Use of Simulation in an Attempt to Enhance Interpretation of a Secondary Data Source in Epidemiologic Mental Health Research
BMC Research Notes. 2010 | Pubmed ID: 20796271
The longitudinal epidemiology of major depressive episodes (MDE) is poorly characterized in most countries. Some potentially relevant data sources may be underutilized because they are not conducive to estimating the most salient epidemiologic parameters. An available data source in Canada provides estimates that are potentially valuable, but that are difficult to apply in clinical or public health practice. For example, weeks depressed in the past year is assessed in this data source whereas episode duration would be of more interest. The goal of this project was to derive, using simulation, more readily interpretable parameter values from the available data.
Delamination of a Highly Cross-linked Polyethylene Liner Associated with Titanium Deposits on the Cobalt-chromium Modular Femoral Head Following Dislocation
The Journal of Bone and Joint Surgery. British Volume. Sep, 2010 | Pubmed ID: 20798454
Retrieval studies of total hip replacements with highly cross-linked ultra-high-molecular-weight polyethylene liners have shown much less surface damage than with conventional ultra-high-molecular-weight polyethylene liners. A recent revision hip replacement for recurrent dislocation undertaken after only five months revealed a highly cross-linked polyethylene liner with a large area of visible delamination. In order to determine the cause of this unusual surface damage, we analysed the bearing surfaces of the cobalt-chromium femoral head and the acetabular liner with scanning electron microscopy, energy dispersive x-ray spectroscopy and optical profilometry. We concluded that the cobalt-chromium modular femoral head had scraped against the titanium acetabular shell during the course of the dislocations and had not only roughened the surface of the femoral head but also transferred deposits of titanium onto it. The largest deposits were 1.6 microm to 4.3 microm proud of the surrounding surface and could lead to increased stresses in the acetabular liner and therefore cause accelerated wear and damage. This case illustrates that dislocations can leave titanium deposits on cobalt-chromium femoral heads and that highly cross-linked ultra-high-molecular-weight polyethylene remains susceptible to surface damage.
Oral Sucrose As an Analgesic Drug for Procedural Pain in Newborn Infants: a Randomised Controlled Trial
Lancet. Oct, 2010 | Pubmed ID: 20817247
Many infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.
Structure Guided Design of 5-arylindazole Glucocorticoid Receptor Agonists and Antagonists
Journal of Medicinal Chemistry. Jun, 2010 | Pubmed ID: 20469868
Glucocorticoid receptor (GR) agonists have been used for more than half a century as the most effective treatment of acute and chronic inflammatory conditions despite serious side effects that accompany their extended use that include glucose intolerance, muscle wasting, skin thinning, and osteoporosis. As a starting point for the identification of GR ligands with an improved therapeutic index, we wished to discover selective nonsteroidal GR agonists and antagonists with simplified structure compared to known GR ligands to serve as starting points for the optimization of dissociated GR modulators. To do so, we selected multiple chemical series by structure guided docking studies and evaluated GR agonist activity. From these efforts we identified 5-arylindazole compounds that showed moderate binding to the glucocorticoid receptor (GR) with clear opportunities for further development. Structure guided optimization was used to design arrays that led to potent GR agonists and antagonists. Several in vitro and in vivo experiments were utilized to demonstrate that GR agonist 23a (GSK9027) had a profile similar to that of a classical steroidal GR agonist.
The Prevalence of Mental Disorders in the Working Population over the Period of Global Economic Crisis
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Sep, 2010 | Pubmed ID: 20840807
The ongoing global economic crisis may have affected people's mental health. This study aimed to, among a sample of the working population, estimate and compare the prevalence of depressive and anxiety disorders in different time intervals from January 2008 to October 2009 and to examine the demographic and socioeconomic correlates of mental disorders.
Pharmacological Preconditioning with GYKI 52466: A Prophylactic Approach to Neuroprotection
Frontiers in Neuroscience. 2010 | Pubmed ID: 20953290
Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This "pharmacological preconditioning" has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA) toxicity in hippocampus. This effect persists well after washout of the drug and may be mediated via inverse agonism of G-protein coupled receptors (GPCRs). Given the amplifying nature of metabotropic modulation, we hypothesized that GYKI 52466 may be effective in reducing seizure severity at doses well below those normally associated with adverse side effects. Here we report that pharmacological preconditioning with low-dose GYKI imparts a significant protection against KA-induced seizures in vivo. GYKI (3 mg/kg, s.c.), 90-180 min prior to high-dose KA, markedly reduced seizure scores, virtually abolished all level 3 and level 4 seizures, and completely suppressed KA-induced hippocampal c-FOS expression. In addition, preconditioned animals exhibited significant reductions in high frequency/high amplitude spiking and ECoG power in the delta, theta, alpha, and beta bands during KA. Adverse behaviors often associated with higher doses of GYKI were not evident during preconditioning. The fact that GYKI is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, suggests that a classical blockade of ionotropic AMPA receptors does not underlie anticonvulsant effects. Low-dose GYKI preconditioning may represent a novel, prophylactic strategy for neuroprotection in a field almost completely devoid of effective pharmaceuticals.
Use of Complementary and Alternative Medicine by Those with a Chronic Disease and the General Population--results of a National Population Based Survey
BMC Complementary and Alternative Medicine. 2010 | Pubmed ID: 20955609
The use of complementary and alternative medicine (CAM) is becoming more common, but population-based descriptions of its patterns of use are lacking. This study aimed to determine the prevalence of CAM use in the general population and for those with asthma, diabetes, epilepsy and migraine.
Simulation Studies of Age-specific Lifetime Major Depression Prevalence
BMC Psychiatry. 2010 | Pubmed ID: 20961404
The lifetime prevalence (LTP) of Major Depressive Disorder (MDD) is the proportion of a population having met criteria for MDD during their life up to the time of assessment. Expectation holds that LTP should increase with age, but this has not usually been observed. Instead, LTP typically increases in the teenage years and twenties, stabilizes in adulthood and then begins to decline in middle age. Proposed explanations for this pattern include: a cohort effect (increasing incidence in more recent birth cohorts), recall failure and/or differential mortality. Declining age-specific incidence may also play a role.
Predictors of the Longitudinal Course of Major Depression in a Canadian Population Sample
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Oct, 2010 | Pubmed ID: 20964946
Most psychiatric epidemiologic studies have used cross-sectional methods, resulting in a lack of information about the longitudinal course of depressive disorders. The objective of our study was to describe the longitudinal epidemiology of major depressive episodes (MDEs) in a Canadian sample using data from the National Population Health Survey (NPHS).
TP53 Mutation Profile in Chronic Lymphocytic Leukemia: Evidence for a Disease Specific Profile from a Comprehensive Analysis of 268 Mutations
Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. Dec, 2010 | Pubmed ID: 20861914
The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p-). Interestingly, trisomy 12 (without 17p-) was only found in one of 60 cases with TP53 mutation (without 17p-) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.
VEGFR2 Heterogeneity and Response to Anti-angiogenic Low Dose Metronomic Cyclophosphamide Treatment
BMC Cancer. 2010 | Pubmed ID: 21159176
Targeting tumor vasculature is a strategy with great promise in the treatment of many cancers. However, anti-angiogenic reagents that target VEGF/VEGFR2 signaling have met with variable results clinically. Among the possible reasons for this may be heterogeneous expression of the target protein.
Pharmacoepidemiology of Benzodiazepine and Sedative-hypnotic Use in a Canadian General Population Cohort During 12 Years of Follow-up
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Dec, 2010 | Pubmed ID: 21172100
benzodiazepines (BDZs) and similar sedative-hypnotics (SSHs) can have both beneficial and adverse effects. Clinical practice guidelines indicate that the course of treatment should usually be brief (a few weeks), but patients often take these medications for longer periods of time. We hypothesized that treatment with antidepressants (ADs) would be associated with a shorter duration of SSHs use as mood and anxiety disorders may underlie the symptoms usually targeted by BDZ treatment.
Reciprocal Effects of Social Support in Major Depression Epidemiology
Clinical Practice and Epidemiology in Mental Health : CP & EMH. 2010 | Pubmed ID: 21253020
The clinical course and epidemiology of major depressive episodes (MDEs) may be influenced by reciprocal interactions between an individual and the social environment. Epidemiological data concerning these interactions may assist with anticipating the clinical needs of depressed patients.
Habitat Selection and the Perceptual Trap
Ecological Applications : a Publication of the Ecological Society of America. Dec, 2010 | Pubmed ID: 21265448
The concept of "ecological traps" was introduced over three decades ago. An ecological trap occurs when, by various mechanisms, low-quality (yielding low fitness) habitat is more attractive than good habitat, thus coaxing individuals to settle there despite a resultant loss of fitness. Empirical work on such traps has increased dramatically in the past decade, but the converse-avoidance of high-quality habitat because it is less attractive, what we term a "perceptual trap" has remained largely unexplored. Even so, depending on conditions (growth rate, strength of habitat preference, and mortality rate), such perceptual traps can be more limiting than ecological traps to population persistence. An example from field experiments with the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) lends empirical support to the concept, and several other potential examples suggest that these traps are perhaps more prevalent than has been appreciated. Because demographic Allee effects are expected to prevent a population from growing sufficiently in a habitat that is avoided, a perceptual trap may persist even though fitness is high. Unlike an ecological trap, which may be negated by increasing habitat quality, biologists will be hard pressed to negate a perceptual trap, which will require determining which cues an animal uses to select high-quality habitat and then devising a means of enhancing those cues so that an animal is lured into the habitat.
The Organization of STI/HIV Risk-taking Among Long-line Fishermen in Bali, Indonesia
International Maritime Health. 2010 | Pubmed ID: 21348013
We report on selected findings of a qualitative social network study investigating STI/HIV-related risk among migrant fishermen based at one of Indonesia's major fishing ports in Bali. Their activities between fishing trips include drinking parties, watching pornographic videos, and visiting brothels, while condom use is rare. While on board, they plan and anticipate these activities and many insert penile implants. These fishermen run a high personal risk of contracting STI/HIV, and, with their circular migration patterns among Indonesian and foreign ports such as Thailand and South Africa, and with visits back to their rural hometowns and wives or girlfriends in Java, there is a serious risk of disease transmission to the general population. This paper argues that the role that social interactions play in HIV/AIDS-related risks should be considered as important as (if not more important than) individual knowledge, attitudes, and practices in the design of effective STI/HIV prevention programs.
PGC-1β Regulates Angiogenesis in Skeletal Muscle
American Journal of Physiology. Endocrinology and Metabolism. Jul, 2011 | Pubmed ID: 21364124
Aerobic metabolism requires oxygen and carbon sources brought to tissues via the vasculature. Metabolically active tissues such as skeletal muscle can regulate blood vessel density to match metabolic needs; however, the molecular cues that coordinate these processes remain poorly understood. Here we report that the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), a potent regulator of mitochondrial biology, induces angiogenesis in skeletal muscle. PGC-1β induces the expression of vascular endothelial growth factor (VEGF) in cell culture and in vivo. The induction of VEGF by PGC-1β requires coactivation of the orphan nuclear receptor estrogen-related receptor-α (ERRα) and is independent of the hypoxia-inducible factor (HIF) pathway. In coculture experiments, overexpression of PGC-1β in skeletal myotubes increases the migration of adjacent endothelial cells, and this depends on VEGF signaling. Transgenic expression of PGC-1β in skeletal myocytes dramatically increases muscular vessel density. Taken together, these data indicate that PGC-1β is a potent regulator of angiogenesis, thus providing a novel link between the regulations of oxidative metabolism and vascular density.
The Association Between Antidepressant Use and Depression Eight Years Later: a National Cohort Study
Journal of Psychiatric Research. Aug, 2011 | Pubmed ID: 21382626
Investigations of the effects of antidepressant treatment for individuals with major depression have focused on short-term outcomes in individuals that meet very specific criteria; however, there is limited knowledge about long-term outcomes associated with antidepressant use in general population samples. This study aimed to investigate the long-term outcomes associated with antidepressant use by focusing on 486 depressed adults in a prospective observational Canadian cohort in 1998/99. We used logistic regression to investigate the association between antidepressant use and depression status 8 years later. Non-random allocation to treatment was accounted for by a propensity-for-treatment model which included thirteen predictors of antidepressant use, including: severity of depressive symptoms, previous episodes of depression (from 1994 to 1997), physical health condition, social support and socio-demographic characteristics. 29% of individuals with major depression reported antidepressant use. After adjusting for propensity for treatment in 1998/99, and antidepressant use from 2000 to 2007, depressed individuals who reported antidepressant use in 1998/99 were less likely to be depressed in 2006/07 compared to those who did not report antidepressant use (OR = 0.36, 95% CI: 0.15-0.88). Amongst individuals with symptoms of major depression, those reporting use of anti-depressants at baseline exhibited improved long-term outcomes in comparison to those who did not report treatment.
Abundance, Diversity and Functional Gene Expression of Denitrifier Communities in Adjacent Riparian and Agricultural Zones
FEMS Microbiology Ecology. Jul, 2011 | Pubmed ID: 21385191
Lands under riparian and agricultural management differ in soil properties, water content, plant species and nutrient content and are therefore expected to influence denitrifier communities, denitrification and nitrous oxide (N(2) O) emissions. Denitrifier community abundance, denitrifier community structure, denitrification gene expression and activity were quantified on three dates in a maize field and adjacent riparian zone. N(2) O emissions were greater in the agricultural zone, whereas complete denitrification to N(2) was greater in the riparian zone. In general, the targeted denitrifier community abundance did not change between agricultural and riparian zones. However, nosZ gene expression was greater in the riparian zone than the agricultural zone. The community structure of nirS-gene-bearing denitrifiers differed in June only, whereas the nirK-gene-bearing community structure differed significantly between the riparian and the agricultural zones at all dates. The nirK-gene-bearing community structure was correlated with soil pH, while no significant correlations were found between nirS-gene-bearing community structure and soil environmental variables or N(2) O emissions, denitrification or denitrifier enzyme activity. The results suggested for the nirK and nirS-gene-bearing communities different factors control abundance vs. community structure. The nirK-gene-bearing community structure was also more responsive than the nirS-gene-bearing community structure to change between the two ecosystems.
A Novel Adoptive Transfer Model of Chronic Lymphocytic Leukemia Suggests a Key Role for T Lymphocytes in the Disease
Blood. May, 2011 | Pubmed ID: 21385850
Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γc(null) mice under the influence of activated CLL-derived T lymphocytes. By co-transferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4(+) T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity.
Strategies for Neoglycan Conjugation to Human Acid α-glucosidase
Bioconjugate Chemistry. Apr, 2011 | Pubmed ID: 21417264
Engineering proteins for selective tissue targeting can improve therapeutic efficacy and reduce undesired side effects. The relatively high dose of recombinant human acid α-glucosidase (rhGAA) required for enzyme replacement therapy of Pompe disease may be attributed to less than optimal muscle uptake via the cation-independent mannose 6-phosphate receptor (CI-MPR). To improve muscle targeting, Zhu et al. (1) conjugated periodate oxidized rhGAA with bis mannose 6-phosphate bearing synthetic glycans and achieved 5-fold greater potency in a murine Pompe efficacy model. In the current study, we systematically evaluated multiple strategies for conjugation based on a structural homology model of GAA. Glycan derivatives containing succinimide, hydrazide, and aminooxy linkers targeting free cysteine, lysines, and N-linked glycosylation sites on rhGAA were prepared and evaluated in vitro and in vivo. A novel conjugation method using enzymatic oxidation was developed to eliminate side oxidation of methionine. Conjugates derived from periodate oxidized rhGAA still displayed the greatest potency in the murine Pompe model. The efficiency of conjugation and its effect on catalytic activity were consistent with predictions based on the structural model and supported its use in guiding selection of appropriate chemistries.
Force Control Deficits in Chronic Stroke: Grip Formation and Release Phases
Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. May, 2011 | Pubmed ID: 21448576
The aim of the study was to develop a novel approach for quantifying stair-stepping in a trajectory tracking task with the goal of understanding how age and stroke-related differences in motor control contribute to force control deficits. Nine stroke participants, nine age-matched controls, and nine young healthy adults performed an isometric gripping task while squeezing, holding, and releasing a cylindrical device. The visual tracking task involved three different rates of force production (5, 10, and 20% maximal force/s). Four outcome measures determined force control deficits: (a) root mean square error, (b) standard deviation, (c) step number, and (d) mean pause duration. Our findings indicate that step number, and especially mean pause duration, differentiated force control deficits in the three groups more effectively than the traditional root mean square error. Moreover, stroke participants showed the largest force control deficits during the grip release phase compared to age-matched and young healthy controls. Importantly, step number and mean pause duration quantified stair-stepping while measuring different constructs than root mean square error. Distinct step and duration interruptions in force modulation by persons post-stroke during the grip release phase provide new information with implications for motor recovery during rehabilitation.
Notes from the Board: President's Message
Clinical Nurse Specialist CNS. May-Jun, 2011 | Pubmed ID: 21483237
PH Responsive Polymer Cushions for Probing Membrane Environment Interactions
Nano Letters. May, 2011 | Pubmed ID: 21500840
A robust and straightforward method for the preparation of lipid membranes upon dynamically responsive polymer cushions is reported. Structural characterization demonstrates that complete, well-packed membranes with tunable mobility can be constructed on the polymeric cushion. With this system, membrane conformational changes induced by cellular cytoskeleton interactions can be modeled. The membrane can be tailored to screen the cushion from changes in pH or allow rapid response to the pH environment by incorporation of protein ion channels. This elementary system offers a means to replicate the conformational changes that occur with the cellular cytoskeleton and has great potential for fundamental biophysical studies of membrane properties and membrane-protein interactions decoupled from the underlying solid support.
Smoking Cessation and Chronic Pain: Patient and Pain Medicine Physician Attitudes
Pain Practice : the Official Journal of World Institute of Pain. Nov-Dec, 2011 | Pubmed ID: 21518246
Although previous studies suggest that the clinical setting of an interdisciplinary pain treatment program may provide an optimal environment to promote smoking cessation, currently available smoking cessation interventions may be less effective for adults with chronic pain due, in part, to unrecognized clinical factors related to chronic pain. The specific aim of this qualitative study was to solicit information from adult smokers with chronic pain participating in an interdisciplinary pain treatment program regarding their perceptions of how smoking affects pain symptoms, and how these beliefs, cognitions, and emotions may either impede or facilitate smoking cessation. Similar information was solicited from a group of pain specialty physicians. The study involved 18 smokers with chronic pain, and seven physicians. Patients reported that smoking was an important coping strategy for pain and distress, primarily by offering an opportunity for distraction and avoidance, respectively. The majority of patients using opioids reported that opioid consumption stimulated smoking. Important barriers were identified toward making a quit attempt during pain treatment including quitting smoking while making changes in opioid use, and perceived difficulty managing multiple treatment-related stressors. Several pain-related benefits of smoking cessation were identified by physicians, but important barriers to providing smoking cessation services were recognized including lack of time and knowledge about how to help patients quit smoking. The findings of this study identified several novel and important clinical factors that should be incorporated into a targeted smoking cessation intervention for adults with chronic pain.
Positive Interspecific Relationship Between Temporal Occurrence and Abundance in Insects
PloS One. 2011 | Pubmed ID: 21533057
One of the most studied macroecological patterns is the interspecific abundance-occupancy relationship, which relates species distribution and abundance across space. Interspecific relationships between temporal distribution and abundance, however, remain largely unexplored. Using data for a natural assemblage of tabanid flies measured daily during spring and summer in Nova Scotia, we found that temporal occurrence (proportion of sampling dates in which a species occurred in an experimental trap) was positively related to temporal mean abundance (number of individuals collected for a species during the study period divided by the total number of sampling dates). Moreover, two models that often describe spatial abundance-occupancy relationships well, the He-Gaston and negative binomial models, explained a high amount of the variation in our temporal data. As for the spatial abundance-occupancy relationship, the (temporal) aggregation parameter, k, emerged as an important component of the hereby named interspecific temporal abundance-occurrence relationship. This may be another case in which a macroecological pattern shows similarities across space and time, and it deserves further research because it may improve our ability to forecast colonization dynamics and biological impacts.
Recall of Recent and More Remote Depressive Episodes in a Prospective Cohort Study
Social Psychiatry and Psychiatric Epidemiology. May, 2011 | Pubmed ID: 21533819
BACKGROUND: In psychiatric epidemiology, symptoms are often assessed retrospectively. This raises concerns about the accuracy of the information recalled. In this study, we sought to examine the level of agreement between survey items assessing recent and more remote depressive episodes. METHODS: Data from the Canadian National Population Health Survey (NPHS) were used. The NPHS is a prospective study following a representative cohort of household residents sampled in 1994 and 1995. Every 2 years, participants are administered the Composite International Diagnostic Interview Short Form for Major Depression (CIDI-SFMD). The 2004 NPHS interview also included items asking about past episodes of depression and diagnoses of depression done by health professionals. We used cross-tabulation and logistic regression to explore the relationship between these responses. RESULTS: Approximately, 90% of respondents with CIDI-SFMD-defined major depressive episodes in the year preceding the 2004 interview also reported lifetime episodes or professional diagnoses of depression in 2004. However, responses to the 2004 lifetime items corresponded less closely to CIDI-SFMD results from the same individuals earlier in the longitudinal survey. Only 40.8% of respondents having the most recently identified episode in 1994 subsequently affirmed a past episode of depression in 2004. CONCLUSIONS: Reporting of depressive episodes diminishes with time, suggesting that retrospective assessment of such episodes may be vulnerable to inaccuracy.
Voluntary Exercise Induces Adult Hippocampal Neurogenesis and BDNF Expression in a Rodent Model of Fetal Alcohol Spectrum Disorders
The European Journal of Neuroscience. May, 2011 | Pubmed ID: 21535455
Alcohol consumption during pregnancy can result in a myriad of health problems in the affected offspring ranging from growth deficiencies to central nervous system impairments that result in cognitive deficits. Adult hippocampal neurogenesis is thought to play a role in cognition (i.e. learning and memory) and can be modulated by extrinsic factors such as alcohol consumption and physical exercise. We examined the impact of voluntary physical exercise on adult hippocampal neurogenesis in a rat model of fetal alcohol spectrum disorders (FASD). Intragastric intubation was used to deliver ethanol to rats in a highly controlled fashion through all three trimester equivalents (i.e. throughout gestation and during the first 10 days of postnatal life). Ethanol-exposed animals and their pair-fed and ad libitum controls were left undisturbed until they reached a young adult stage at which point they had free access to a running wheel for 12 days. Prenatal and early postnatal ethanol exposure altered cell proliferation in young adult female rats and increased early neuronal maturation without affecting cell survival in the dentate gyrus (DG) of the hippocampus. Voluntary wheel running increased cell proliferation, neuronal maturation and cell survival as well as levels of brain-derived neurotrophic factor in the DG of both ethanol-exposed female rats and their pair-fed and ad libitum controls. These results indicate that the capacity of the brain to respond to exercise is not impaired in this model of FASD, highlighting the potential therapeutic value of physical exercise for this developmental disorder.
Characterization of Recombinant Human Carboxylesterases: Fluorescein Diacetate As a Probe Substrate for Human Carboxylesterase 2
Drug Metabolism and Disposition: the Biological Fate of Chemicals. Aug, 2011 | Pubmed ID: 21540359
Human carboxylesterase (CES) 1 and CES2 are members of the serine hydrolase superfamily, and both exhibit broad substrate specificity and are involved in xenobiotic and endobiotic metabolism. Although expression of CES1 and CES2 occurs in several organs, their expression in liver and small intestine is predominantly attributed to CES1 and CES2, respectively. We successfully expressed CES1 form b (CES1-b) and form c (CES1-c) as well as CES2 in baculovirus-infected High Five insect cells. With 4-nitrophenyl acetate (4-NPA) as the probe substrate, the K(m) values of recombinant CES1-b and CES2 matched those of human liver microsomes (HLM) and human intestinal microsomes (HIM) with approximately 200 and 180 μM, respectively. Bis(4-nitrophenyl) phosphate potently inhibited 4-NPA hydrolysis by HLM, CES1-b, CES1-c, HIM, and CES2 with IC(50) values less than 1 μM. With fluorescein diacetate (FD) as the substrate, the K(m) values were similar for all enzyme systems, with the exception of CES1-b, which was slightly lower; however, the V(max) values for HIM and CES2 were 39.5 and 14.6 μmol · mg(-1) · min(-1), respectively, which were at least 50-fold higher than those of CES1-b or CES1-c. Loperamide potently inhibited HLM, HIM, and CES2 with similar IC(50) values of approximately 1 μM. Substrate specificity was compared between human tissues and recombinant enzymes. The data suggest the following: 1) FD is a probe substrate for CES2; 2) CES1-b is the predominant form in human liver; and 3) recombinant CES1-b and CES2 expressed in insect cells are functionally consistent with native carboxylesterases expressed in human liver and intestine, respectively.
Clinical Effectiveness, Construct and Assessment
Journal of Affective Disorders. Aug, 2011 | Pubmed ID: 21561665
In an era of contention about the efficacy of antidepressants, the concept of clinical effectiveness has surfaced as a basic tenet of real-world practice. The concept of clinical effectiveness can lead to important insights into the treatment of depression and, by acting as an organizing concept for research, can help studies better focus on obtaining information necessary to improve clinical practice.
Evidence for a Macromolecular Complex in Poor Prognosis CLL That Contains CD38, CD49d, CD44 and MMP-9
British Journal of Haematology. Jul, 2011 | Pubmed ID: 21569005
Progressive chronic lymphocytic leukaemia is characterized by the accumulation of neoplastic B-cells in the tissues and correlates with the expression of prognostic biomarkers, such as CD38, CD49d and matrix metalloproteinase-9 (MMP9), which are involved in migration and tissue invasion. In this study we investigated the physical relationship between these molecules and demonstrated that CD38, CD49d, MMP9 and CD44 were physically associated in a supramolecular cell surface complex. Our findings provide a molecular basis for the correlation between expression of these proteins and prognosis and, as the complex is not present in normal B-cells, suggest a novel leukaemia-specific therapeutic target.
Operationalizing Frailty Among Older Residents of Assisted Living Facilities
BMC Geriatrics. 2011 | Pubmed ID: 21569509
Frailty in later life is viewed as a state of heightened vulnerability to poor outcomes. The utility of frailty as a measure of vulnerability in the assisted living (AL) population remains unexplored. We examined the feasibility and predictive accuracy of two different interpretations of the Cardiovascular Health Study (CHS) frailty criteria in a population-based sample of AL residents.
A Plant Growth-promoting Pseudomonad is Closely Related to the Pseudomonas Syringae Complex of Plant Pathogens
FEMS Microbiology Ecology. Sep, 2011 | Pubmed ID: 21609343
Pseudomonas putida GR12-2 is well known as a plant growth-promoting rhizobacterium; however, phylogenetic analysis using the 16S rRNA gene and four housekeeping genes indicated that this strain forms a monophyletic group with the Pseudomonas syringae complex, which is composed of several species of plant pathogens. On the basis of these sequence analyses, we suggest that P. putida GR12-2 be redesignated as P. syringae GR12-2. To compare the ecological roles of P. syringae GR12-2 with its close relatives P. syringae pathovar (pv.) tomato DC3000 and P. syringae pv. syringae B728a, we investigated their ability to cause disease and promote plant growth. When introduced on tobacco or tomato leaves, P. syringae GR12-2 was unable to elicit a hypersensitive response or cause disease, which are characteristic responses of P. syringae DC3000 and B728a, nor were type III secretion system genes required for virulence detected in P. syringae GR12-2 by PCR or DNA hybridization. In contrast to P. syringae GR12-2, neither of the phytopathogens was able to promote root growth when inoculated onto canola seeds. Although commensals and nonpathogens have been reported among the strains of the P. syringae complex, P. syringae GR12-2 is a mutualist and a phytostimulator.
Re: "Job Strain and the Risk of Depression: is Reporting Biased?"
American Journal of Epidemiology. Jul, 2011 | Pubmed ID: 21636629
Solitary Extramedullary Plasmacytoma of the Thyroid Involved by Papillary Carcinoma: a Case Report and Review of the Literature
Endocrine Pathology. Sep, 2011 | Pubmed ID: 21643773
Role of ω3 Longchain Polyunsaturated Fatty Acids in Reducing Cardio-Metabolic Risk Factors
Endocrine, Metabolic & Immune Disorders Drug Targets. Jun, 2011 | Pubmed ID: 21651471
Cardiovascular disease is the leading cause of mortality in many economically developed nations, and its incidence is increasing at a rapid rate in emerging economies. Diet and lifestyle issues are closely associated with a myriad of cardiovascular disease risk factors including abnormal plasma lipids, hypertension, insulin resistance, diabetes and obesity, suggesting that diet-based approaches may be of benefit. Omega-3 longchain-polyunsaturated fatty acids (ω3 LC-PUFA) are increasingly being used in the prevention and management of several cardiovascular risk factors. Both the ω3 and ω6 PUFA families are considered essential, as the human body is itself unable to synthesize them. The conversion of the two precursor fatty acids - linoleic acid (18:2ω6) and α-linoleic acid (α18:3ω3) - of these two pathways to longer (≥C(20)) PUFA is inefficient. Although there is an abundance of ω6 PUFA in the food supply; in many populations the relative intake of ω3 LC-PUFA is low with health authorities advocating increased consumption. Fish oil, rich in eicosapentaenoic (EPA, 20:5ω3) and docosahexaenoic (DHA, 22:6ω3) acids, has been found to cause a modest reduction in blood pressure at a dose level of >3g/d both in untreated and treated hypertensives. Whilst a multitude of mechanisms may contribute to the blood pressure lowering action of ω3 LC-PUFA, improved vascular endothelial cell function appears to play a central role. Recent studies which evaluated the potential benefits of fish oil in type-2 diabetes have helped to alleviate concerns raised in some previous studies which used relatively large dose (5-8 g/d) and reported a worsening of glycemic control. Several meta-analyses have confirmed that the most consistent action of ω3 LC-PUFA in insulin resistance and type-2 diabetes is the reduction in triglycerides. In some studies, fish oil has been found to cause a small rise in LDL-cholesterol, but a change in the LDL particle size, from the smaller more atherogenic form to the larger, less damaging particle size, have also been noted. ω3 LC-PUFA are effective modulators of the inflammation that accompanies several cardio-metabolic abnormalities. Taking into consideration the pleiotropic nature of their actions, it can be concluded that dietary supplementation with ω3 LC-PUFA will lead to improvements in cardio-metabolic health parameters. These fatty acids pose only minor side effects and more importantly, do not interact adversely with the common drug therapies used in the management and treatment of hypertension, dyslipidemia, type-2 diabetes, and obesity/metabolic syndrome, but in some instances work synergistically, thereby providing additional cardiovascular benefits.
Notes from the Board: President's Message
Clinical Nurse Specialist CNS. Jul-Aug, 2011 | Pubmed ID: 21654367
Support-person Promotion of a Smoking Quitline: a Randomized Controlled Trial
American Journal of Preventive Medicine. Jul, 2011 | Pubmed ID: 21665059
Quitlines and other evidence-based cessation treatments are greatly underutilized by smokers, limiting their public health impact. Social support is correlated with successful cessation. Thus, efforts targeting the social network of smokers could be a potential avenue to promote quitline utilization.
Effects of Casoxin 4 on Morphine Inhibition of Small Animal Intestinal Contractility and Gut Transit in the Mouse
Clinical and Experimental Gastroenterology. 2011 | Pubmed ID: 21694869
Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1) characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2) test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.
Estimates of the Treated Prevalence of Bipolar Disorders by Mental Health Services in the General Population: Comparison of Results from Administrative and Health Survey Data
Chronic Diseases and Injuries in Canada. Jun, 2011 | Pubmed ID: 21733350
Informed provision of population mental health services requires accurate estimates of disease burden.
Predictors of 1-year Outcomes of Major Depressive Disorder Among Individuals with a Lifetime Diagnosis: a Population-based Study
Psychological Medicine. Jul, 2011 | Pubmed ID: 21740627
BACKGROUND: Examining predictors of the outcomes of major depressive disorder (MDD) is important for clinical practice and population health. There are few population-based longitudinal studies on this topic. The objectives of this study were to (1) estimate the proportions of persistent and recurrent MDD among those with MDD over 1 year, and (2) identify demographic, socio-economic, workplace psychosocial and clinical factors associated with the outcomes.MethodFrom a population-based longitudinal study of the working population, participants with a lifetime diagnosis of MDD were selected (n=834). They were classified into two groups: those with and those without current MDD. The proportions of 1-year persistence and recurrence of MDD were estimated. MDD was assessed by the World Health Organization (WHO) Composite International Diagnostic Interview, CIDI-Auto 2.1, by telephone. RESULTS: The proportions of persistent and recurrent MDD in 1 year were 38.5% [95% confidence interval (CI) 31.1-46.5] and 13.3% (95% CI 10.2-17.1) respectively. Long working hours, negative thinking and having co-morbid social phobia were predictive of persistence of MDD. Perceived work-family conflict, the severity of a major depressive episode and symptoms of depressed mood were significantly associated with the recurrence of MDD. CONCLUSIONS: Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different. More large longitudinal studies on this topic are needed so that clinicians may predict potential outcomes based on the clinical profile and provide interventions accordingly. They may also take clinical action to change relevant psychosocial factors to minimize the chance of persistence and/or recurrence of MDD.
Metabolic and Neurological Complications of Second-generation Antipsychotic Use in Children: a Systematic Review and Meta-analysis of Randomized Controlled Trials
Drug Safety : an International Journal of Medical Toxicology and Drug Experience. Aug, 2011 | Pubmed ID: 21751826
Available evidence indicates that the use of antipsychotics, especially second-generation antipsychotics (SGAs), for children with mental health disorders has increased dramatically. Given the demonstrated metabolic and neurological adverse effects seen in adult patients on these medications, detailed evaluation of the risk for these adverse effects in children is appropriate.
Weight Gain in Relation to Major Depression and Antidepressant Medication Use
Journal of Affective Disorders. Nov, 2011 | Pubmed ID: 21774992
Previous studies have linked major depressive episodes (MDEs) to obesity. The association may be partially mediated by antidepressant medication use. In the current study we examine changes in weight and BMI in relation to MDE and antidepressant use in a general population cohort.
Decreased Metalloprotease 9 Induction, Cardiac Fibrosis, and Higher Autophagy After Pressure Overload in Mice Lacking the Transcriptional Regulator P8
American Journal of Physiology. Cell Physiology. Nov, 2011 | Pubmed ID: 21775709
Left ventricular remodeling, including the deposition of excess extracellular matrix, is key to the pathogenesis of heart failure. The stress-inducible transcriptional regulator p8 is increased in failing human hearts and is required both for agonist-stimulated cardiomyocyte hypertrophy and for cardiac fibroblasts matrix metalloprotease-9 (MMP9) induction. In the heart, upregulation of autophagy is an adaptive response to stress and plays a causative role in cardiomyopathies. We have recently shown that p8 ablation in cardiac cells upregulates autophagy and that, in vivo, loss of p8 results in a decrease of cardiac function. Here we investigated the effects of p8 genetic deletion in mediating adverse myocardial remodeling. Unstressed p8-/- mouse hearts manifested complex alterations in the expression of fibrosis markers. In addition, these mice displayed elevated autophagy and apoptosis compared with p8+/+ mice. Transverse aortic constriction (TAC) induced left ventricular p8 expression in p8+/+ mice. Pressure overload caused left ventricular remodeling in both genotypes, however, p8-/- mice showed less cardiac fibrosis induction. Consistent with this, although MMP9 induction was attenuated in the p8-/- mice, induction of MMP2 and MMP3 were strikingly upregulated while TIMP2 was downregulated. Left ventricular autophagy increased after TAC and was significantly higher in the p8-/- mice. Thus p8-deletion results in reduced collagen fibrosis after TAC, but in turn, is associated with a detrimental higher increase in autophagy. These findings suggest a role for p8 in regulating in vivo key signaling pathways involved in the pathogenesis of heart failure.
Gastrointestinal Nematode Control Practices on Lowland Sheep Farms in Ireland with Reference to Selection for Anthelmintic Resistance
Irish Veterinary Journal. 2011 | Pubmed ID: 21777491
ABSTRACT: Gastrointestinal parasitism is a widely recognised problem in sheep production, particularly for lambs. While anthelmintics have a pivotal role in controlling the effects of parasites, there is a paucity of data on how farmers use anthelmintics. A representative sample of Irish lowland farmers were surveyed regarding their parasite control practices and risk factors that may contribute to the development of anthelmintic resistance. Questionnaires were distributed to 166 lowland Irish sheep producers. The vast majority of respondents treated their sheep with anthelmintics. Lambs were the cohort treated most frequently, the majority of farmers followed a set programme as opposed to treating at sign of disease. A substantial proportion (61%) administered four or more treatments to lambs in a 'normal' year. Departures from best practice in anthelmintic administration that would encourage the development of anthelmintic resistance were observed. In conclusion, in the light of anthelmintic resistance, there is a need for a greater awareness of the principles that underpin the sustainable use of anthelmintics and practices that preserve anthelmintic efficacy should be given a very high priority in the design of helminth control programmes on each farm. To this end, given that veterinary practitioners and agricultural advisors were considered to be the farmer's most popular information resource, the capacity of these professions to communicate information relating to best practice in parasite control should be targeted.
Fabrication and Characterization of Rare-earth-doped Nanostructures on Surfaces
ACS Nano. Aug, 2011 | Pubmed ID: 21780743
This article presents a simple and practical means to produce rare-earth-based nanostructures, as well as a combined characterization of structure and optical properties in situ. A nanosphere lithography strategy combined with surface chemistry enables the production of arrays of β-NaYF(4):Yb,Er nanorings inlaid in an octadecyltrichlorosilane matrix. These arrays of nanorings are produced over the entire support, such as a 1 cm(2) glass coverslip. The dimension of nanorings can be varied by changing the deposition conditions. A home-constructed, multifunctional microscope integrating atomic force microscopy, near-field scanning optical microscopy, and far-field optical microscopy and spectroscopy is utilized to characterize the nanostructures. This in situ and combined characterization is important for rare-earth-containing nanomaterials in order to correlate local structure with upconversion photoluminescence. Knowledge gained from the investigation should facilitate materials design and optimization, for instance, in the context of photovoltaic devices and biofluorescent probes.
Tradeoffs Amongst Fatigue, Wear, and Oxidation Resistance of Cross-linked Ultra-high Molecular Weight Polyethylene
Journal of the Mechanical Behavior of Biomedical Materials. Oct, 2011 | Pubmed ID: 21783113
This study evaluated the tradeoffs amongst fatigue crack propagation resistance, wear resistance, and oxidative stability in a wide variety of clinically-relevant cross-linked ultra-high molecular weight polyethylene. Highly cross-linked re-melted materials showed good oxidation and wear performance, but diminished fatigue crack propagation resistance. Highly cross-linked annealed materials showed good wear and fatigue performance, but poor oxidation resistance. Moderately cross-linked re-melted materials showed good oxidation resistance, but moderate wear and fatigue resistance. Increasing radiation dose increased wear resistance but decreased fatigue crack propagation resistance. Annealing reduced fatigue resistance less than re-melting, but left materials susceptible to oxidation. This appears to occur because annealing below the melting temperature after cross-linking increased the volume fraction and size of lamellae, but failed to neutralize all free radicals. Alternately, re-melting after cross-linking appeared to eliminate free radicals, but, restricted by the network of cross-links, the re-formed lamellae were fewer and smaller in size which resulted in poor fatigue crack propagation resistance. This is the first study to simultaneously evaluate fatigue crack propagation, wear, oxidation, and microstructure in a wide variety of clinically-relevant ultra-high. The tradeoff we have shown in fatigue, wear, and oxidation performance is critical to the material's long-term success in total joint replacements.
Role of ω3 Longchain Polyunsaturated Fatty Acids in Reducing Cardio-metabolic Risk Factors
Endocrine, Metabolic & Immune Disorders Drug Targets. Sep, 2011 | Pubmed ID: 21831036
Cardiovascular disease is the leading cause of mortality in many economically developed nations, and its incidence is increasing at a rapid rate in emerging economies. Diet and lifestyle issues are closely associated with a myriad of cardiovascular disease risk factors including abnormal plasma lipids, hypertension, insulin resistance, diabetes and obesity, suggesting that diet-based approaches may be of benefit. Omega-3 longchain-polyunsaturated fatty acids (ω3 LC-PUFA) are increasingly being used in the prevention and management of several cardiovascular risk factors. Both the ω3 and ω6 PUFA families are considered essential, as the human body is itself unable to synthesize them. The conversion of the two precursor fatty acids - linoleic acid (18:2ω6) and α-linoleic acid (α18:3ω3) - of these two pathways to longer (≥C(20)) PUFA is inefficient. Although there is an abundance of ω6 PUFA in the food supply; in many populations the relative intake of ω3 LC-PUFA is low with health authorities advocating increased consumption. Fish oil, rich in eicosapentaenoic (EPA, 20:5ω3) and docosahexaenoic (DHA, 22:6ω3) acids, has been found to cause a modest reduction in blood pressure at a dose level of >3g/d both in untreated and treated hypertensives. Whilst a multitude of mechanisms may contribute to the blood pressure lowering action of ω3 LC-PUFA, improved vascular endothelial cell function appears to play a central role. Recent studies which evaluated the potential benefits of fish oil in type-2 diabetes have helped to alleviate concerns raised in some previous studies which used relatively large dose (5-8 g/d) and reported a worsening of glycemic control. Several meta-analyses have confirmed that the most consistent action of ω3 LC-PUFA in insulin resistance and type-2 diabetes is the reduction in triglycerides. In some studies, fish oil has been found to cause a small rise in LDL-cholesterol, but a change in the LDL particle size, from the smaller more atherogenic form to the larger, less damaging particle size, have also been noted. ω3 LC-PUFA are effective modulators of the inflammation that accompanies several cardio-metabolic abnormalities. Taking into consideration the pleiotropic nature of their actions, it can be concluded that dietary supplementation with ω3 LC-PUFA will lead to improvements in cardio-metabolic health parameters. These fatty acids pose only minor side effects and more importantly, do not interact adversely with the common drug therapies used in the management and treatment of hypertension, dyslipidemia, type-2 diabetes, and obesity/metabolic syndrome, but in some instances work synergistically, thereby providing additional cardiovascular benefits.
Major Depression is a Risk Factor for Shorter Time to First Cigarette Irrespective of the Number of Cigarettes Smoked Per Day: Evidence from a National Population Health Survey
Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Nov, 2011 | Pubmed ID: 21832274
We assessed whether major depression (MD) predicts progression of nicotine dependence (ND) as measured by reduction in the time to first cigarette (TTFC) after waking and the roles of the number of cigarettes smoked per day (CPD) and stress as explanatory variables of this association.
Differential Associations Between Sensory Response Patterns and Language, Social, and Communication Measures in Children with Autism or Other Developmental Disabilities
Journal of Speech, Language, and Hearing Research : JSLHR. Dec, 2011 | Pubmed ID: 21862675
To examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities (DDs).
Predictors of Occupancy Trend Across Spatial Scale
Conservation Biology : the Journal of the Society for Conservation Biology. Dec, 2011 | Pubmed ID: 21883465
Many explorations of extinction probability have had a global focus, yet it is unclear whether variables that explain the probability of extinction at large spatial extents are the same as those at small spatial extents. Thus, we used nearly annual presence-absence records for the most recent 40 years of a 110-year data set from Palenque, Mexico, an area with ongoing deforestation, to explore which of >200 species of birds have probabilities of extirpation that are likely to increase. We assessed associations between long-term trends in species presence (i.e., detection in a given year) and body size, geographic range size, diet, dependence on forest cover, taxonomy, and ecological specialization. Our response variable was the estimated slope of a weighted logistic regression for each species. We assessed the relative strength of each predictor by means of a model ranking scheme. Several variables associated with high extinction probability at global extents, such as large body size or small geographic range size, were not associated with occurrence of birds over time at our site. Body size was associated with species loss at Palenque, but occurrence trends of both very large and very small species, particularly the latter, have declined, or the species have been extirpated. We found no association between declining occurrence trend and geographic range size, yet decline correlated with whether a species depends on forest (mean occupancy trend =-0.0380, 0.0263, and 0.0186 for, respectively, species with high, intermediate, or low dependence on forest) and with complex combinations of diet and foraging strata (e.g., occurrence of canopy insectivores and terrestrial omnivores has increased, whereas occurrence of mid-level frugivores and terrestrial granivores has decreased). Our findings emphasize that analyses of local areas are necessary to explicate extirpation risk at various spatial extents.
Perceived Needs for and Use of Workplace Accommodations by Individuals with a Depressive And/or Anxiety Disorder
Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. Nov, 2011 | Pubmed ID: 21918478
To estimate the percentages of need for and use of workplace mental health accommodations, and to identify factors related to the use of accommodations.
Self-regulatory Fatigue in Hematologic Malignancies: Impact on Quality of Life, Coping, and Adherence to Medical Recommendations
International Journal of Behavioral Medicine. Sep, 2011 | Pubmed ID: 21928059
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. PURPOSE: This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. METHODS: Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. RESULTS: Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. CONCLUSION: These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.
Rethinking Recommendations for Screening for Depression in Primary Care
CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. Sep, 2011 | Pubmed ID: 21930744
Torque Teno Virus 10 Isolated by Genome Amplification Techniques from a Patient with Concomitant Chronic Lymphocytic Leukemia and Polycythemia Vera
Molecular Medicine (Cambridge, Mass.). Sep, 2011 | Pubmed ID: 21953418
An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods, we identified a new isolate (BIS8-17) of torque teno virus (TTV) 10. The presence of BIS8-17 in the original plasma was confirmed by PCR, validating the approach since TTV is a known plasma virus. Subsequent PCR testing of plasmas from additional patients showed that BIS8-17 had a similar incidence (~20%) in CLL (n=48) or PV (n=10) as compared to healthy controls (n=52). CLL cells do not harbor BIS8-17 as PCR did not detect it in CLL peripheral blood genomic DNA (n=20). CLL patient clinical outcome or prognostic markers (IGHV mutation, CD38, or ZAP-70) did not correlate with BIS8-17 infection. Although not causative to our knowledge, this is the first reported isolation and detection of TTV in either CLL or PV. TTV could serve as a co-virus with another infectious agent or TTV variant with rearranged genetic components that contributes to disease pathogenesis. These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease.
Altered Adult Hippocampal Neuronal Maturation in a Rat Model of Fetal Alcohol Syndrome
Brain Research. Apr, 2011 | Pubmed ID: 21303667
Exposure to ethanol during pregnancy can be devastating to the developing nervous system, leading to significant central nervous system dysfunction. The hippocampus, one of the two brain regions where neurogenesis persists into adulthood, is particularly sensitive to the teratogenic effects of ethanol. In the present study, we tested a rat model of fetal alcohol syndrome (FAS) with ethanol administered via gavage throughout all three trimester equivalents. Subsequently, we assessed cell proliferation, as well as neuronal survival, and differentiation in the dentate gyrus of the hippocampus of adolescent (35 days old), young adult (60 days old) and adult (90 days old) Sprague-Dawley rats. Using both extrinsic (bromodeoxyuridine) and intrinsic (Ki-67) markers, we observed no significant alterations in cell proliferation and survival in ethanol-exposed animals when compared with their pair-fed and ad libitum controls. However, we detected a significant increase in the number of new immature neurons in animals that were exposed to ethanol throughout all three trimester equivalents. This result might reflect a compensatory mechanism to counteract the deleterious effects of prenatal ethanol exposure or an ethanol-induced arrest of the neurogenic process at the early neuronal maturation stages. Taken together these results indicate that exposure to ethanol during the period of brain development causes a long-lasting dysregulation of the neurogenic process, a mechanism that might contribute, at least in part, to the hippocampal deficits that have been reported in rodent models of FAS.
Evaluation of TP53 Mutations with the AmpliChip P53 Research Test in Chronic Lymphocytic Leukemia: Correlation with Clinical Outcome and Gene Expression Profiling
Genes, Chromosomes & Cancer. Apr, 2011 | Pubmed ID: 21319261
Given that TP53 alterations predict prognosis and response to therapy in chronic lymphocytic leukemia (CLL), screening for TP53 mutations has an increasing role in patient management. TP53 direct sequencing is a time-consuming method, while the AmpliChip p53 Research Test is a novel non time-consuming microarray-based resequencing assay and queries Exons 2-11. We evaluated the impact of TP53 mutations on clinical outcome by analyzing 98 untreated CLL using the AmpliChip p53 Research Test and direct sequencing and performed microarrays analysis on TP53 mutated and/or deleted cases. The AmpliChip p53 Research Test detected 17 mutations in 14 patients (17.3%); a significant association between TP53 mutations and del(17p) was recorded. From a clinical standpoint, a higher percentage of mutation was found in CLL with unfavorable outcome (17.2% vs. 7.1% in progressive vs. stable cases). Detection of TP53 mutations by the AmpliChip p53 Research Test was associated with a significantly worse survival (P = 0.0002). Comparison of the array and direct sequencing tests showed that the p53 Research Test detected more mutations, although it failed to identify two microdeletions. Finally, microarrays analysis showed a more distinctive signature associated with del(17p) than with TP53 mutations, likely due to a concomitant gene dosage effect. The AmpliChip p53 Research Test is a straightforward method that bears prognostic value. This study confirms a high percentage of TP53 mutations in CLL with unfavorable outcome and a significant association between TP53 aberrations and del(17p). Finally, specific gene expression profiles are recognized for TP53 alterations.
Evaluation of TP53 Mutations with the AmpliChip P53 Research Test in Chronic Lymphocytic Leukemia: Correlation with Clinical Outcome and Gene Expression Profiling
Genes, Chromosomes & Cancer. Jan, 2011 | Pubmed ID: 21234939
Given that TP53 alterations predict prognosis and response to therapy in chronic lymphocytic leukemia (CLL), screening for TP53 mutations has an increasing role in patient management. TP53 direct sequencing is a time-consuming method, while the AmpliChip p53 Research Test is a novel non time-consuming microarray-based resequencing assay and queries Exons 2-11. We evaluated the impact of TP53 mutations on clinical outcome by analyzing 98 untreated CLL using the AmpliChip p53 Research Test and direct sequencing and performed microarrays analysis on TP53 mutated and/or deleted cases. The AmpliChip p53 Research Test detected 17 mutations in 14 patients (17.3%); a significant association between TP53 mutations and del(17p) was recorded. From a clinical standpoint, a higher percentage of mutation was found in CLL with unfavorable outcome (17.2% vs. 7.1% in progressive vs. stable cases). Detection of TP53 mutations by the AmpliChip p53 Research Test was associated with a significantly worse survival (P = 0.0002). Comparison of the array and direct sequencing tests showed that the p53 Research Test detected more mutations, although it failed to identify two microdeletions. Finally, microarrays analysis showed a more distinctive signature associated with del(17p) than with TP53 mutations, likely due to a concomitant gene dosage effect. The AmpliChip p53 Research Test is a straightforward method that bears prognostic value. This study confirms a high percentage of TP53 mutations in CLL with unfavorable outcome and a significant association between TP53 aberrations and del(17p). Finally, specific gene expression profiles are recognized for TP53 alterations. © 2011 Wiley-Liss, Inc.
A Stripe-to-droplet Transition Driven by Conformational Transitions in a Binary Lipid-lipopolymer Mixture at the Air-water Interface
Langmuir : the ACS Journal of Surfaces and Colloids. Mar, 2011 | Pubmed ID: 21244080
We report the observation of an unusual stripe-droplet transition in precompressed Langmuir monolayers consisting of mixtures of poly(ethylene) glycol (PEG) amphiphiles and phospholipids. This highly reproducible and fully reversible transition occurs at approximately zero surface pressure during expansion (or compression) of the monolayer following initial compression into a two-dimensional solid phase. It is characterized by spontaneous emergence of an extended, disordered stripe-like morphology from an optically homogeneous phase during gradual expansion. These stripe patterns appear as a transient feature and continuously progress, involving gradual coarsening and ultimate transformation into a droplet morphology upon further expansion. Furthermore, varying relative concentrations of the two amphiphiles and utilizing amphiphiles with considerably longer ethylene glycol headgroups reveal that this pattern evolution occurs in narrow concentration regimes, values of which depend on ethylene oxide headgroup size. These morphological transitions are reminiscent of those seen during a passage through a critical point by variations in thermodynamic parameters (e.g., temperature or pressure) as well as those involving spinodal decomposition. While the precise mechanism cannot be ascertained using present experiments alone, our observations can be reconciled in terms of modulations in competing interactions prompted by the pancake-mushroom-brush conformational transitions of the ethylene glycol headgroup. This in turn suggests that the conformational degree of freedom represents an independent order parameter, or a switch, which can induce large-scale structural reorganization in amphiphilic monolayers. Because molecular conformational changes are pervasive in biological membranes, we speculate that such conformational transition-induced pattern evolution might provide a physical mechanism by which membrane processes are amplified.
Could Genetic Determinants of Inner Ear Anomalies Be a Factor for the Development of Idiopathic Scoliosis?
Medical Hypotheses. Mar, 2011 | Pubmed ID: 21146321
Adolescent idiopathic scoliosis (AIS) is a condition characterized by a three-dimensional structural deformity of the spine. It is the most common type of spine deformity occurring in children aged 10 to maturity. Although the etiology of AIS still remains unknown, the role of genetic factors in the development of idiopathic scoliosis is widely accepted. However, to date no causative genes of AIS have been identified. Recently, the semicircular canals, which are part of the inner ear, were found to be morphologically abnormal in idiopathic scoliosis patients. Here we hypothesized that genetic predisposition to inner ear anomalies in AIS patients may be a strong factor in the generation of idiopathic scoliosis. The proposed idea is that gene defects could impair the development of the semicircular canals. A malformation of semicircular canals might affect the transmission of sensory signal about rotational movement of the body to the central nervous system; leading to an alteration in the neuronal circuit of balance. This will in turn affect body posture and results in the initiation of the curvature of the spine. This hypothesis may provide new insights in the understanding of the pathophysiologic mechanisms of idiopathic scoliosis. It can also offer hopes for potential early prediction of scoliosis.
A Quantitative Analysis of Suspected Environmental Causes of MS
The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. Jan, 2011 | Pubmed ID: 21156437
Multiple sclerosis (MS) is a disease with purported environmental causes. Consistent correlations have been found in various settings for latitude, smoking exposure, sunlight, and vitamin D deficiency. We analysed the contribution of various environmental factors to the risk of developing MS from a population perspective.
Willingness of Cancer Patients to Help Family Members to Quit Smoking
Psycho-oncology. Jul, 2011 | Pubmed ID: 20878860
The impact of social support on successful smoking cessation has been well documented. However, little is known about whether personal experience with cancer may motivate cancer survivors to support smoking cessation among their family members and friends. As a first step in this line of research, we sought to explore interest in playing a supportive role for smoking cessation as well as correlates of such interest among cancer survivors.
X-ray and Biochemical Analysis of N370S Mutant Human Acid β-glucosidase
The Journal of Biological Chemistry. Jan, 2011 | Pubmed ID: 20980263
Gaucher disease is caused by mutations in the enzyme acid β-glucosidase (GCase), the most common of which is the substitution of serine for asparagine at residue 370 (N370S). To characterize the nature of this mutation, we expressed human N370S GCase in insect cells and compared the x-ray structure and biochemical properties of the purified protein with that of the recombinant human GCase (imiglucerase, Cerezyme®). The x-ray structure of N370S mutant acid β-glucosidase at acidic and neutral pH values indicates that the overall folding of the N370S mutant is identical to that of recombinant GCase. Subtle differences were observed in the conformation of a flexible loop at the active site and in the hydrogen bonding ability of aromatic residues on this loop with residue 370 and the catalytic residues Glu-235 and Glu-340. Circular dichroism spectroscopy showed a pH-dependent change in the environment of tryptophan residues in imiglucerase that is absent in N370S GCase. The mutant protein was catalytically deficient with reduced V(max) and increased K(m) values for the substrate p-nitrophenyl-β-D-glucopyranoside and reduced sensitivity to competitive inhibitors. N370S GCase was more stable to thermal denaturation and had an increased lysosomal half-life compared with imiglucerase following uptake into macrophages. The competitive inhibitor N-(n-nonyl)deoxynojirimycin increased lysosomal levels of both N370S and imiglucerase 2-3-fold by reducing lysosomal degradation. Overall, these data indicate that the N370S mutation results in a normally folded but less flexible protein with reduced catalytic activity compared with imiglucerase.
CYP4F Enzymes Are Responsible for the Elimination of Fingolimod (FTY720), a Novel Treatment of Relapsing Multiple Sclerosis
Drug Metabolism and Disposition: the Biological Fate of Chemicals. Feb, 2011 | Pubmed ID: 21045201
Fingolimod (FTY720, Gilenya, 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol) is a novel drug recently approved in the United States for the oral treatment of relapsing multiple sclerosis. The compound is eliminated predominantly by ω-hydroxylation, followed by further oxidation. The ω-hydroxylation was the major metabolic pathway in human liver microsomes (HLM). The enzyme kinetics in HLM were characterized by a Michaelis-Menten affinity constant (K(m)) of 183 μM and a maximum velocity (V(max)) of 1847 pmol/(min · mg). Rates of fingolimod metabolism by a panel of HLM from individual donors showed no correlation with marker activities of any of the major drug-metabolizing cytochrome P450 (P450) enzymes or of flavin-containing monooxygenase (FMO). Among 21 recombinant human P450 enzymes and FMO3, only CYP4F2 (and to some extent CYP4F3B) produced metabolite profiles similar to those in HLM. Ketoconazole, known to inhibit not only CYP3A but also CYP4F2, was an inhibitor of fingolimod metabolism in HLM with an inhibition constant (K(i)) of 0.74 μM (and by recombinant CYP4F2 with an IC(50) of 1.6 μM), whereas there was only a slight inhibition found with azamulin and none with troleandomycin. An antibody against CYP4F2 was able to inhibit the metabolism of fingolimod almost completely in HLM, whereas antibodies specific to CYP2D6, CYP2E1, and CYP3A4 did not show significant inhibition. Combining the results of these four enzyme phenotyping approaches, we demonstrated that CYP4F2 and possibly other enzymes of the CYP4F subfamily (e.g., CYP4F3B) are the major enzymes responsible for the ω-hydroxylation of fingolimod, the main elimination pathway of the drug in vivo.
Stable Linkage Disequilibrium Owing to Sexual Antagonism
Proceedings. Biological Sciences / The Royal Society. Mar, 2011 | Pubmed ID: 20861051
Linkage disequilibrium (LD) is an association between genetic loci that is typically transient. Here, we identify a previously overlooked cause of stable LD that may be pervasive: sexual antagonism. This form of selection produces unequal allele frequencies in males and females each generation, which upon admixture at fertilization give rise to an excess of haplotypes that couple male-beneficial with male-beneficial and female-beneficial with female-beneficial alleles. Under sexual antagonism, LD is obtained for all recombination frequencies in the absence of epistasis. The extent of LD is highest at low recombination and for stronger selection. We provide a partition of the total LD into distinct components and compare our result for sexual antagonism with Li and Nei's model of LD owing to population subdivision. Given the frequent observation of sexually antagonistic selection in natural populations and the number of traits that are often involved, these results suggest a major contribution of sexual antagonism to genomic structure.
The Impact of Smoking on Outcomes Among Patients Undergoing Hematopoietic SCT for the Treatment of Acute Leukemia
Bone Marrow Transplantation. Feb, 2011 | Pubmed ID: 20479707
A paucity of research exists examining the potential impact of tobacco use on cancer treatment outcomes, especially among patients treated with hematopoietic SCT (HSCT). A retrospective cohort study design was used to examine the impact of smoking on duration of hospitalization and overall survival among 148 consecutive patients undergoing HSCT for treatment of acute leukemia from 1999 to 2005. Of the 148 patients, 15% reported current smoking, 30% former smoking, and 55% never used tobacco. Patients were followed for a median 3.5 years (interquartile range=2.1-5.5). Compared to no history of smoking, current smoking was associated with worse pre-HSCT pulmonary function tests (P<0.02 in each case), more days hospitalization (46.2 days versus 25.7 days, P=0.025), and poorer overall survival (hazard ratio (HR)=1.88; 95% CI 1.09-3.25). Results were similar after multivariate adjustment, although the association with overall survival attenuated slightly (HR=1.75; 95% CI 1.00-3.06). Current smoking appears to adversely affect the number of days hospitalized post HSCT and overall survival. Translational research focused on interventions to promote tobacco cessation may lead to improved HSCT outcomes.
Muscle Performance and Physical Function Are Associated with Voluntary Rate of Neuromuscular Activation in Older Adults
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. Jan, 2011 | Pubmed ID: 20829294
Muscle power is related to mobility function in older adults, and effective power production requires rapid neuromuscular activation. Accordingly, this study examines the association of neuromuscular activation rate with muscle performance in persons of different age and mobility function.
Interventions Targeting Attention in Young Children with Autism
American Journal of Speech-language Pathology / American Speech-Language-Hearing Association. Feb, 2011 | Pubmed ID: 20739632
The ability to focus and sustain one's attention is critical for learning. Children with autism demonstrate unusual characteristics of attention from infancy. It is reasonable to assume that early anomalies in attention influence a child's developmental trajectories. Therapeutic interventions for autism often focus on core features of autism such as communication and socialization, while very few interventions specifically address attention. The purpose of this article is to provide clinicians a description of attention characteristics in children with autism and discuss interventions thought to improve attention.
Associations Between Mammographic Density and Serum and Dietary Cholesterol
Breast Cancer Research and Treatment. Jan, 2011 | Pubmed ID: 20464480
Although high mammographic density is a risk factor for postmenopausal breast cancer, its etiology remains unclear. We examined whether serum and dietary cholesterol, which increase breast cancer risk and are involved in endogenous estrogen formation, were associated with increased mammographic density. We conducted a cross-sectional analysis of 302 healthy, sedentary postmenopausal women, aged 50-74 years, enrolled in the Alberta Physical Activity and Breast Cancer Prevention Trial between 2003 and 2006. In multiple linear regression models, no significant associations were observed between serum lipids and percent density or dense tissue area (Percent density: b (change in square root percent density per unit change in cholesterol level) = -0.06 (95%CI = -0.26 to 0.13); b = 0.06 (95%CI = -0.48 to 0.61); and b = -0.11 (95%CI = -0.33 to 0.10) for total cholesterol, high-, and low-density lipoprotein, respectively; similar results found for dense area). Alcohol consumption modified the association between triglycerides and percent density (>1 drink/day: b = -0.94 (95%CI = -1.79 to -0.10); ≤ 1 drink/day: b = 0.19 (95%CI = -0.12 to 0.50); and no alcohol consumption: b = 0.15 (95%CI = -0.44 to 0.73). We found no evidence indicating any association between dietary and serum cholesterol levels and mammographic density.
Diabetes, Cardiovascular Disease, and Health Care Use in People with and Without Schizophrenia
European Psychiatry : the Journal of the Association of European Psychiatrists. Jul-Aug, 2011 | Pubmed ID: 20634043
To compare the prevalence of cardiovascular risk factors (CV-RF) and disease (CV-D) and health care use in people with and without schizophrenia. SUBJECTS/MATERIALS AND METHODS: Data from the Canadian Community Health Survey (CCHS), cycle 3.1, were used. Prevalence of CV-RF, CV-D, and health care use were compared in those with and without schizophrenia using logistic regression analysis. Sampling weights and bootstrap variance estimates were used to account for survey design.
Multimodal 3D Imaging of Cells and Tissue, Bridging the Gap Between Clinical and Research Microscopy
Annals of Biomedical Engineering. Oct, 2011 | Pubmed ID: 21984512
Absorption dyes are widely used in traditional cytology and pathology clinical practice, while fluorophores and nanoparticles are more often used in biologic research. Optical projection tomographic microscopy (OPTM) is a platform technology that can image the same specimen in multiple modes in 3D, providing morphologic and molecular information concurrently and in exact co-registration. The depth-of-field of a high numerical aperture objective is extended by scanning the focal plane through the sample to generate an optical projection image. Samples of cells or tissue are brought into the OPTM instrument through a microcapillary tube filled with optical index-matching gel. Multiple optical projection images are taken from different perspectives by rotating the tube. Computed tomography (CT) algorithms are applied to these optical projection images to reconstruct 3D structure of the sample. Image segmentation and analysis based on these 3D images provide quantitative biosignatures for cancer diagnosis that represents a clear improvement over conventional 2D image analysis. In this article, we introduce the OPTM platform, optical Cell-CT, and Tissue-CT instruments, and some applications using these OPTM instruments.
In Vitro Validation of Acetyltransferase Activity of GlmU As an Antibacterial Target in Haemophilus Influenzae
The Journal of Biological Chemistry. Nov, 2011 | Pubmed ID: 21984832
GlmU is a bifunctional enzyme that is essential for bacterial growth, converting D-glucosamine 1-phosphate into UDP-GlcNAc via acetylation and subsequent uridyl transfer. A biochemical screen of AstraZeneca's compound library using GlmU of Escherichia coli identified novel sulfonamide inhibitors of the acetyltransferase reaction. Steady-state kinetics, ligand-observe NMR, isothermal titration calorimetry, and x-ray crystallography showed that the inhibitors were competitive with acetyl-CoA substrate. Iterative chemistry efforts improved biochemical potency against gram-negative isozymes 300-fold and afforded antimicrobial activity against a strain of Haemophilus influenzae lacking its major efflux pump. Inhibition of precursor incorporation into bacterial macromolecules was consistent with the antimicrobial activity being caused by disruption of peptidoglycan and fatty acid biosyntheses. Isolation and characterization of two different resistant mutant strains identified the GlmU acetyltransferase domain as the molecular target. These data, along with x-ray co-crystal structures, confirmed the binding mode of the inhibitors and explained their relative lack of potency against gram-positive GlmU isozymes. This is the first example of antimicrobial compounds mediating their growth inhibitory effects specifically via GlmU.
VEGFR2 Expression and TGF-β Signaling in Initial and Recurrent High-grade Human Glioma
Oncology. 2011 | Pubmed ID: 21985798
Bevacizumab has promising activity against glioma, although reasons for poor efficacy and variable response rates in certain patients are unclear. Vascular endothelial growth factor receptor 2 (VEGFR2) is heterogeneously expressed within the microvasculature of various malignancies. Moreover, transforming growth factor β (TGF-β), a negative prognostic factor for glioma, is intimately involved in angiogenesis including VEGFR2 regulation. Our objective was to associate expression of VEGFR2 and TGF-β activity with clinicopathological features of human glioma.
Muscle Power Failure in Mobility-limited Older Adults: Preserved Single Fiber Function Despite Lower Whole Muscle Size, Quality and Rate of Neuromuscular Activation
European Journal of Applied Physiology. Oct, 2011 | Pubmed ID: 22005960
This study investigated the physiological and gender determinants of the age-related loss of muscle power in 31 healthy middle-aged adults (aged 40-55 years), 28 healthy older adults (70-85 years) and 34 mobility-limited older adults (70-85 years). We hypothesized that leg extensor muscle power would be significantly lower in mobility-limited elders relative to both healthy groups and sought to characterize the physiological mechanisms associated with the reduction of muscle power with aging. Computed tomography was utilized to assess mid-thigh body composition and calculate specific muscle power and strength. Surface electromyography was used to assess rate of neuromuscular activation and muscle biopsies were taken to evaluate single muscle fiber contractile properties. Peak muscle power, strength, muscle cross-sectional area, specific muscle power and rate of neuromuscular activation were significantly lower among mobility-limited elders compared to both healthy groups (P ≤ 0.05). Mobility-limited older participants had greater deposits of intermuscular adipose tissue (P < 0.001). Single fiber contractile properties of type I and type IIA muscle fibers were preserved in mobility-limited elders relative to both healthy groups. Male gender was associated with greater decrements in peak and specific muscle power among mobility-limited participants. Impairments in the rate of neuromuscular activation and concomitant reductions in muscle quality are important physiological mechanisms contributing to muscle power deficits and mobility limitations. The dissociation between age-related changes at the whole muscle and single fiber level suggest that, even among older adults with overt mobility problems, contractile properties of surviving muscle fibers are preserved in an attempt to maintain overall muscle function.
Intestinal Passage of Microencapsulated Fish Oil in Rats Following Oral Administration
Food & Function. Nov, 2011 | Pubmed ID: 22006459
Fish oil labelled with [(14)C-linolenin] tracer was orally administered by gavage as an oil-water mixture (free oil) or as an oil-in-water emulsion formulation (microencapsulated oil) to fasted rats. Groups of rats were then given food after gavage or alternatively not fed to examine the effect of food on intestinal passage. Feeding after gavage drives lumenal free oil faster through the gastrointestinal (GI) tract. Microencapsulation slows down the lumenal progression in the GI tract with feeding. Non-feeding also slows down the lumenal progress of free oil in the GI tract but this is not influenced by microencapsulation. Analysis of the relative distribution of the label along the GI tract tissue wall showed that the upper small intestine was the main site of label accumulation in the GI tract. Of the oil that remained in the lumen, there was slight protection against early uptake and metabolism in the stomach and upper GI tract in rats that were either fed or not fed after dosing when microencapsulated oil was administered. Microencapsulation increased the levels of radiolabel in the liver and blood. The primary organ for accumulation of radiolabel for both free and microencapsulated oils in rats that were fed or fasted after dosing was the liver.
The Pharmacoepidemiology of Antipsychotics for Adults with Schizophrenia in Canada, 2005 to 2009
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Oct, 2011 | Pubmed ID: 22014696
To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009.
A Population-Based Longitudinal Community Study of Major Depression and Migraine
Headache. Nov, 2011 | Pubmed ID: 22084834
Objective.- To examine whether major depressive episodes (MDEs) are associated with an increased risk of migraine in the general population and to examine whether migraine is associated with an increase risk of MDE. Background.- Population-based cross-sectional studies have consistently reported an association between migraine and depression. However, longitudinal studies about this potentially bidirectional association are inconsistent. Methods.- This retrospective cohort study used 12 years of follow-up data from the Canadian National Population Health Survey (15,254 respondents, age >12). Stratified analysis, logistic regression, and proportional hazard modeling were used to quantify the effect of migraine on subsequent MDE status and vice versa. Results.- After adjusting for sex, age, and other chronic health conditions, respondents with migraine were 60% more likely (HR 1.6, 95% confidence interval 1.3-1.9) to develop MDE compared with those without migraine. Similarly adjusting for sex and age, respondents with MDE were 40% more likely (HR 1.4, 95% confidence interval 1.0-1.9) to develop migraine compared with those without MDE. However, the latter association disappeared after adjustment for stress and childhood trauma. Conclusions.- The current study provides substantial evidence that migraine is associated with the later development of MDEs, but does not provide strong causal evidence of an association in the other direction. Environmental factors such as childhood trauma and stress may shape the expression of this bidirectional relationship; however, the precise underlying mechanisms are not yet known.
Intramuscular Cavernous Haemangioma of the Triceps
International Journal of Surgery Case Reports. 2011 | Pubmed ID: 22096691
Haemangiomas are one of the most common soft tissue tumours comprising 7% of all benign tumours. Vascular malformations are often confused with haemangiomas. The etiology is unknown. They are common in infancy and childhood and females are more commonly affected. These tumours may be superficial or deep, and deeply seated lesions, are difficult to diagnose clinically and hence require radiographic assessment. Deep-seated haemangiomas are usually intramuscular, although intra-articular synovial haemangiomas also occur. The commonest anatomic site is the lower limb.Despite their vascular origin, haemangiomas do not metastasize or undergo malignant transformation. Many treatment modalities for the symptomatic haemangioma are available but surgical excision is the preferred treatment. We present an unusual case of a dumb-bell intramuscular haemangioma involving the triceps and extending into the cubital tunnel of the elbow, distinguish between haemangiomas and vascular malformations and emphasize the importance of surgical technique in ensuring ulnar nerve safety.
Solitary Langerhans Histiocytosis of the Thyroid Gland: A Case Report and Literature Review
Head and Neck Pathology. Dec, 2011 | Pubmed ID: 22198822
Langerhans cell histiocytosis (LCH) is a rare disease of antigen presenting cells, with an incidence rate of 4.0-5.4 per 1 million individuals. The most common endocrinological manifestation of classical LCH is associated with the posterior pituitary, presenting as Diabetes Insipidus. However, LCH can affect multiple organs and classification is based on the body system involvement. The disease is confirmed by electron microscopy or immunohistochemical reactivity of histiocytes to CD1a and/or S100. LCH rarely involves the thyroid gland, and management of such disease is controversial. Current literature documents 65 English language reported cases of LCH involving the thyroid gland. We present an unusual case of LCH of the thyroid gland, with variable diagnoses on fine needle aspiration (FNA) cytology, and literature review of all English reported cases.
Mortality Associated with Major Depression in a Canadian Community Cohort
Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Nov, 2011 | Pubmed ID: 22114920
Prior studies have reported that major depressive episodes (MDEs) are associated with elevated mortality. However, the association has not always persisted after adjustment for other mortality risk factors. In our study, we examine this issue using data from a longitudinal Canadian study (the National Population Health Survey [NPHS]). The NPHS included a more comprehensive set of mortality determinants than prior studies, allowing a more comprehensive assessment of the effect of MDEs on mortality.
Incidence and Predictors of Pacemaker Placement After Surgical Ablation for Atrial Fibrillation
The Annals of Thoracic Surgery. Dec, 2011 | Pubmed ID: 22115221
Bradyarrhythmia requiring pacemaker placement is a relatively common complication after surgical ablation for atrial fibrillation (AF). We report our experience with surgical ablation procedures using various energy modalities and lesion sets in an attempt to identify the risk factors associated with postoperative pacemaker requirement.
The Pharmacoepidemiology of Antipsychotic Medications for Canadian Children and Adolescents: 2005-2009
Journal of Child and Adolescent Psychopharmacology. Dec, 2011 | Pubmed ID: 22136092
To describe the frequency and trends of use of antipsychotics in Canadian children and adolescents from 2005 to 2009.
Predictors of Long-term Prognosis of Depression
CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. Nov, 2011 | Pubmed ID: 22025655
Many people with depression experience repeated episodes. Previous research into the predictors of chronic depression has focused primarily on the clinical features of the disease; however, little is known about the broader spectrum of sociodemographic and health factors inherent in its development. Our aim was to identify factors associated with a long-term negative prognosis of depression.
Repetitive Transcranial Magnetic Stimulation of Motor Cortex After Stroke: a Focused Review
American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. Mar, 2012 | Pubmed ID: 22042336
ABSTRACT: Repetitive Transcranial Magnetic Stimulation (rTMS) is known to modulate cortical excitability and has thus been suggested to be a therapeutic approach for improving the efficacy of rehabilitation for motor recovery after stroke. In addition to producing effects on cortical excitability, stroke may affect the balance of transcallosal inhibitory pathways between motor primary areas in both hemispheres: the affected hemisphere (AH) may be disrupted not only by the infarct itself but also by the resulting asymmetric inhibition from the unaffected hemisphere, further reducing the excitability of the AH. Conceptually, therefore, rTMS could be used therapeutically to restore the balance of interhemispheric inhibition after stroke. rTMS has been used in two ways: low-frequency stimulation (≤1 Hz) to the motor cortex of the unaffected hemisphere to reduce the excitability of the contralesional hemisphere or high-frequency stimulation (>1 Hz) to the motor cortex of the AH to increase excitability of the ipsilesional hemisphere. The purpose of this systematic review is to collate evidence regarding the safety and efficacy of high-frequency rTMS to the motor cortex of the AH. The studies included investigated the concurrent effects of rTMS on the excitability of corticospinal pathways and upper-limb motor function in adults after stroke. This review suggests that rTMS applied to the AH is a safe technique and could be considered an effective approach for modulating brain function and contributing to motor recovery after stroke. Although the studies included in this review provide important information, double-blinded, sham-controlled Phase II and Phase III clinical trials with larger sample sizes are needed to validate this novel therapeutic approach.
PGC-1 Coactivators in the Cardiovascular System
Trends in Endocrinology and Metabolism: TEM. Feb, 2012 | Pubmed ID: 22047951
The beating heart consumes more ATP per weight than any other organ. The machineries required for this are many and complex. Fuel and oxygen must be transported via the vasculature, absorbed by cardiomyocytes, broken down, and regulated to match cellular demands. Much of this occurs in mitochondria, which comprise fully one third of cardiac mass. The PGC-1 proteins are transcriptional coactivators that have emerged as powerful orchestrators of these numerous processes, ensuring their proper coregulation in response to intracellular and extracellular cues. An important role for PGC-1s in cardiac function has been revealed over the past few years, and more recently interest in their role in the vasculature has been burgeoning. We review this literature, focusing on recent developments.
A Population-based Study of Prevalence and Adherence Trends in Average Risk Colorectal Cancer Screening, 1997 to 2008
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012 | Pubmed ID: 22144500
Increasing colorectal cancer screening (CRCS) is important for attaining the Healthy People 2020 goal of reducing CRC-related morbidity and mortality. Evaluating CRCS trends can help identify shifts in CRCS, and specific groups that might be targeted for CRCS.
Mentor and Protégé: a Mutually Beneficial Relationship
The American Journal of Nursing. Jan, 2012 | Pubmed ID: 22207537
Epilepsy is Associated with Unmet Health Care Needs Compared to the General Population Despite Higher Health Resource Utilization-A Canadian Population-based Study
Epilepsia. Feb, 2012 | Pubmed ID: 22221191
Purpose: (1) To determine whether health resource utilization (HRU) and unmet health care needs differ for individuals with epilepsy compared to the general population or to those with another chronic condition (asthma, diabetes, migraine); and (2) to assess the association among epilepsy status, sociodemographic variables and HRU. Methods: Data on HRU were assessed using the 2001-2005 Canadian Community Health Surveys, a nationally representative population-based survey. Weighted estimates of association were produced as adjusted odds ratio with 95% confidence intervals, and logistic regression was used to explore the association between sociodemographic variables and HRU in those with epilepsy. All data on disease status, HRU, and unmet health care needs were self-reported. Key Findings: Individuals with epilepsy had the highest rate of hospitalizations and the highest mean number of consultations with physicians. Despite higher rates of consultation with psychologists and social workers compared to the general population, those with epilepsy were significantly more likely to say they had unmet mental health care needs. People with epilepsy were also less likely to use dental services compared to the general population. Epilepsy was a significant predictor of HRU in logistic regression models. Significance: Given the prevalence of psychiatric comorbidities in those with epilepsy, it is concerning that this group perceives unmet mental health care needs. It is also troublesome that there was decreased utilization of dental health care resources in those with epilepsy considering that these patients are more likely to have poor oral health. Although individuals with epilepsy use more health care services than the general population, this increase appears to be insufficient to address their health care needs.
Perampanel in Parkinson Disease Fluctuations: a Double-blind Randomized Trial with Placebo and Entacapone
Clinical Neuropharmacology. Jan, 2012 | Pubmed ID: 22222634
Perampanel is a selective and noncompetitive α-amino-3-hydroxy-5-methylisoxazole propionic acid-type glutamate receptor antagonist that improves motor symptoms in animal models of Parkinson disease (PD). The aim of this study was to assess the efficacy and tolerability of perampanel in L-dopa-treated patients with moderately severe PD and motor fluctuations using an active comparator study design.
Business Mergers and Acquisitions and the Risk of Mental Disorders: a Population-based Study
Occupational and Environmental Medicine. Jan, 2012 | Pubmed ID: 22228854
ObjectivesMergers and acquisitions (M&A) activities are increasing and may negatively affect workers mental health. However, the impact of M&A on the risk of developing a mental disorder, rather than psychiatric symptoms, has not been investigated. The objectives of this study were to estimate and compare the 12-month incidence of depressive and anxiety disorders in workers who had and who had not experienced M&A in the last year.MethodsEmployees aged 25 and 64 years old were randomly selected from the community and were followed for 1 year (n=3280). Questions about their experience in M&A in the past 12 months were asked. WHO's Composite International Diagnostic Interview-Auto 2.1 was used to assess depressive and anxiety disorders. The 12-month prevalence and 1-year incidence of mental disorders were estimated and compared in relation to M&A.ResultsParticipants who were exposed to M&A had a significant higher 1-year incidence of generalised anxiety disorder (GAD) (6.7%) than the unexposed (2.4%). They were not different in the incidence of major depressive disorder. The exposed participants were 2.8 times more likely to have had a GAD than others and were about 2.4 times more likely to have developed any anxiety disorders over 1 year.ConclusionsM&A may lead to increased risk of GAD, which may, in return, evolve into major depression. Governments, employers and health professionals should be aware of this and work out plans to reduce the negative health outcomes of M&A.
Persistent Heavy Smoking As Risk Factor for Major Depression (MD) Incidence - Evidence from a Longitudinal Canadian Cohort of the National Population Health Survey
Journal of Psychiatric Research. Jan, 2012 | Pubmed ID: 22277304
BACKGROUND: Reports of bidirectional associations between smoking and major depression (MD) have been interpreted as providing evidence for confounding by shared-vulnerability factors (SV) that predispose individuals to both conditions. If this is true, then smoking cessation may not reduce the risk of MD. From clinical practice and public health perspectives, the long-term outcomes associated with smoking persistence and cessation are potentially important and deserve exploration. To this end, the 12-year risk of MD in persistent heavy smokers and abstainers who were former-heavy smokers with and without adjustment for potential confounders were compared. METHODS: Follow-up data from the National Population Health Survey (NPHS) was used. Multinomial logistic (ML) models were fit to identify potential confounders. Using proportional hazard (PH) models, unadjusted and adjusted hazard ratios (HRs) for MD outcome were estimated for different smoking patterns. RESULTS: The unadjusted HR relating the risk of MD among current-heavy versus former-heavy smokers was 4.3 (95% CI: 2.6-6.9, p < 0.001). Current-heavy smoking predicted onset of MD (HR = 3.1, 95% CI: 1.9-5.2, p < 0.001) even after adjustment for age, sex and stress - the main confounders. However, this was not the case for the never, former-light, and current-light categories. Evidence of decreased risk of MD among former-heavy relative to current-heavy smokers as function of smoking cessation maintenance time was also found. CONCLUSIONS: Contrary to common beliefs about the benefits of smoking for mental health, our results suggest that current-heavy rather than ever-heavy smoking is a major determinant of MD risk and point towards the benefits of smoking cessation maintenance.
Upper-extremity H-reflex Measurement Post-stroke: Reliability and Inter-limb Differences
Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Jan, 2012 | Pubmed ID: 22277759
OBJECTIVE: To establish test-retest reliability of flexor carpi radialis (FCR) H-reflexes in non-disabled and stroke participants. We also investigated inter-limb differences and effects of chronicity post-stroke compared to non-disabled group and age-related effects in the non-disabled group. METHODS: Sixteen chronic stroke and twenty-two non-disabled participants were recruited. Bilateral FCR H-reflexes were tested on two separate days by stimulating the median nerve and recording surface electromyography responses. FCR recruitment curves were plotted for H-reflex (H) and motor (M) waves and normalized as a percentage of maximal M-wave (ordinate) and motor threshold (abscissa). STATISTICS: Intraclass correlation coefficients [two-way mixed model-ICC (1, 2)], one-way ANOVA, Bland-Altman plots, standard error of measurement (SEM), and smallest real difference (SRD). RESULTS: ICCs ranged from 0.55 to 0.95 (stroke) and 0.69-0.88 (non-disabled). SEM% (% of the mean) ranged from 9% to 24% (stroke) and 18-38% (non-disabled); SRD% ranged from 18% to 66% (stroke) and 6% to 50% (non-disabled). H-reflex amplitude and slope were greater in the paretic vs. non-paretic arm post-stroke (p=0.07 and 0.01, respectively) and the paretic arm vs. non-disabled participants (p=0.007 and 0.002, respectively). Stroke participants with longer chronicity (mean 9.4years) revealed a significantly greater Hslp/Mslp on the paretic side compared to shorter chronicity (2.5years; p=0.05). Mean Hslp/Mslp was significantly greater in the young (mean 29years) compared to the older group (62years; p=0.045). CONCLUSIONS: These results establish reliability of FCR H-reflexes in stroke and non-disabled participants. SEM and SRD measurements can be used to interpret recovery patterns and longitudinal effects of therapeutic interventions. SIGNIFICANCE: FCR H-reflex amplitude and slope can be reliably measured and used to investigate neurophysiological mechanisms of motor recovery post-stroke.
Sporadic Medullary Thyroid Carcinoma with a Pedunculated Intraluminal Internal Jugular Vein Recurrence: A Case Report and Literature Review
International Journal of Surgery Case Reports. 2012 | Pubmed ID: 22288056
Medullary thyroid carcinoma (MTC) is an uncommon usually slowly progressing neuroendocrine tumour that arises from calcitonin (CT) producing parafollicular C cells of the thyroid gland. It accounts for approximately 5% of all thyroid cancers. The majority of MTCs are sporadic (75%) whilst 25% are part of the MEN 2 hereditary syndrome (MEN 2A and MEN 2B and familial MTC). Mutations of the proto-oncogene, RET (Rearranged during Transfection), found on chromosome 10q11, are present in more than 95% of hereditary MTCs and about 25% of sporadic MTCs. MTC metastasizes primarily via lymphatic spread, to central, and lateral nodal neck compartments and the anterior and superior mediastinum. Distant haematogenous spread targets the lungs, liver, bone and brain, and is presumed to be secondary to a lymphatic pathway. There are no previously documented reports of a focal pedunculated metastases located within the jugular vein. We present the first reported case of a metastatic MTC lesion found in the right internal jugular vein in a man with recurrent MTC.
Inhibitors of Acetyltransferase Domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 1: Hit to Lead Evaluation of a Novel Arylsulfonamide Series
Bioorganic & Medicinal Chemistry Letters. Feb, 2012 | Pubmed ID: 22297115
A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40.
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Management of Patients with Mood Disorders and Select Comorbid Medical Conditions
Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. Feb, 2012 | Pubmed ID: 22303525
Medical comorbidity in patients with mood disorders has become an increasingly important clinical and global public health issue. Several specific medical conditions are associated with an increased risk of mood disorders, and conversely, mood disorders are associated with increased morbidity and mortality in patients with specific medical disorders.
Utilization of General and Specialized Cardiac Care by People With Schizophrenia
Psychiatric Services (Washington, D.C.). Feb, 2012 | Pubmed ID: 22307876
OBJECTIVE: Whether access to primary and specialist care has an impact on treatment for people with schizophrenia and comorbid cardiac disease is unclear. The objective of this study was to compare use of general health care and specialized cardiac care by people with schizophrenia and by the rest of the population. METHODS: A population-based period-prevalence study was conducted and included adults (N=2,310,391) in Alberta, Canada, by using administrative databases. People with schizophrenia were identified based on billing codes; all others served as the comparator cohort. Multivariable logistic regression analyses were conducted to compare claims for general (general practitioner visits) health care, urgent and emergent (emergency department visits and hospitalizations) health services, and specialized cardiac (cardiologist visits, revascularization) care. RESULTS: Individuals with schizophrenia (N=28,755) had a higher prevalence of coronary artery disease than those without schizophrenia (N=2,281,636) (20% versus 14%) and were more likely than those without schizophrenia to visit a general practitioner more than four times per year (76% versus 47%; adjusted odds ratio [AOR]=3.60, 95% confidence interval [CI]=3.49-3.71). In contrast, individuals with schizophrenia and coronary artery disease were less likely to visit a cardiologist (50% versus 59%; AOR=. 76, 95% CI=.72-.80) or undergo coronary revascularization (6% versus 12%; AOR=. 55, 95% CI=.49-.61). CONCLUSIONS: In this large population-based study, individuals with schizophrenia were less likely to visit cardiologists or undergo revascularization than were people without schizophrenia. Opportunities exist for better assessment and management of cardiovascular disease and risk factors among people with schizophrenia. (Psychiatric Services doi: 10.1176/appi.ps.201000363).
Tobacco Cessation Intervention During Pregnancy Among Alaska Native Women
Journal of Cancer Education : the Official Journal of the American Association for Cancer Education. Feb, 2012 | Pubmed ID: 22311690
This paper describes a community-based participatory research program with Alaska Native people addressing a community need to reduce tobacco use among pregnant women and children. Tobacco use during pregnancy among Alaska Native women is described along with development of a community partnership, findings from a pilot tobacco cessation intervention, current work, and future directions. Among Alaska Native women residing in the Yukon Kuskokwim Delta region of western Alaska, the prevalence of tobacco use (cigarette smoking and/or use of smokeless tobacco) during pregnancy is 79%. Results from a pilot intervention study targeting pregnant women indicated low rates of participation and less than optimal tobacco abstinence outcomes. Developing alternative strategies to reach pregnant women and to enhance the efficacy of interventions is a community priority, and future directions are offered.
Arogenate Dehydratase Isoenzymes Profoundly and Differentially Modulate Carbon Flux into Lignins
The Journal of Biological Chemistry. Feb, 2012 | Pubmed ID: 22311980
How carbon flux differentially occurs in vascular plants following photosynthesis for protein formation, phenylpropanoid metabolism (i.e. lignins), and other metabolic processes is not well understood. Having previously discovered/deduced that a six-membered arogenate dehydratase (ADT 1-6) gene family encodes the final step in Phe biosynthesis in Arabidopsis thaliana, this raised the fascinating question whether individual ADT isoenzymes (or combinations thereof) differentially modulated carbon flux to lignins, proteins, etc. If so, unlike all other lignin pathway manipulations which target cell wall/cytosolic processes, this would be the first example of a plastid (chloroplast) associated metabolic process influencing cell-wall formation. Homozygous T-DNA insertion lines were thus obtained for 5 of the 6 ADTs, these being used to generate double, triple and quadruple knockouts (KOs) in different combinations. The various mutants so obtained gave phenotypes with profound but distinct reductions in lignin amounts, encompassing a range spanning from near to wild type levels to reductions of up to ~68%. In the various KOs, there were also marked changes in guaiacyl:syringyl (G:S) ratios ranging from ~3:1 to 1:1, respectively, these being rationalized due to differential carbon flux into vascular bundles (vb) versus that of fiber cells. Laser-microscope dissection/ pyrolysis GC/MS, histochemical staining/lignin analyses, and pADT::GUS-localization, suggested that ADT5 preferentially affects carbon flux into the vb, whereas the adt3456 knockout additionally greatly reduced carbon flux into fiber cells. This plastid-localized metabolic step can thus profoundly differentially affect carbon flux into lignins in distinct anatomical regions, and provides incisive new insight into different factors affecting G:S ratios and lignin primary structure.
Rising Prevalence of Vascular Comorbidities in Multiple Sclerosis: Validation of Administrative Definitions for Diabetes, Hypertension, and Hyperlipidemia
Multiple Sclerosis (Houndmills, Basingstoke, England). Feb, 2012 | Pubmed ID: 22328682
Background: Despite the importance of comorbidity in multiple sclerosis (MS), methods for comorbidity assessment in MS are poorly developed.Objective: We validated and applied administrative case definitions for diabetes, hypertension, and hyperlipidemia in MS.Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for diabetes, hypertension, and hyperlipidemia were derived using hospital, physician, and prescription claims, and validated in 430 persons with MS. We examined temporal trends in the age-adjusted prevalence of these conditions from 1984-2006.Results: Agreement between various case definitions and medical records ranged from kappa (κ) =0.51-0.69 for diabetes, κ =0.21-0.71 for hyperlipidemia, and κ =0.52-0.75 for hypertension. The 2005 age-adjusted prevalence of diabetes was similar in the MS (7.62%) and general populations (8.31%; prevalence ratio [PR] 0.91; 0.81-1.03). The age-adjusted prevalence did not differ for hypertension (MS: 20.8% versus general: 22.5% [PR 0.91; 0.78-1.06]), or hyperlipidemia (MS: 13.8% versus general: 15.2% [PR 0.90; 0.67-1.22]). The prevalence of all conditions rose in both populations over the study period.Conclusion: Administrative data are a valid means of tracking diabetes, hypertension, and hyperlipidemia in MS. The prevalence of these comorbidities is similar in the MS and general populations.
Gastroenterologists and Accountable Care Organizations
Gastrointestinal Endoscopy Clinics of North America. Jan, 2012 | Pubmed ID: 22099711
Within the Patient Protection and Affordable Care Act of 2010 is a provision setting up a program for the implementation of accountable care organizations (ACOs). This article explains the proposed ACO model and discusses major implications regarding this model of health care reform including the following: What will it take to implement the program successfully? What are the opportunities for savings under the model? What are the potential downfalls of the program as proposed? What impact would the implementation of an ACO have on the practice of gastroenterology?
Review: Depression is Associated with an Increased Risk of Stroke in Adults
Evidence-based Mental Health. Feb, 2012 | Pubmed ID: 22108247
Anxiety- and Depression-like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: Protective Effects of Voluntary Physical Exercise
Neuropharmacology. Mar, 2012 | Pubmed ID: 22019722
Prenatal ethanol exposure can damage the developing nervous system, producing long-lasting impairments in both brain structure and function. In this study we analyzed how exposure to this teratogen during the period of brain development affects the intracellular redox state in the brain as well as the development of anxiety- and depressive-like phenotypes. Furthermore, we also tested whether aerobic exercise might have therapeutic potential for fetal alcohol spectrum disorders (FASD) by increasing neuronal antioxidant capacity and/or by alleviating ethanol-induced behavioral deficits. Sprague-Dawley rats were administered ethanol across all three-trimester equivalents (i.e., throughout gestation and during the first 10 days of postnatal life). Ethanol-exposed and control animals were assigned to either sedentary or running groups at postnatal day (PND) 48. Runners had free access to a running wheel for 12 days and at PND 60 anxiety- and depressive-like behaviors were assessed. Perinatal ethanol exposure resulted in the occurrence of depressive and anxiety-like behaviors in adult rats without affecting their locomotor activity. Voluntary wheel running reversed the depressive-like behaviors in ethanol-exposed males, but not in ethanol-exposed females. Levels of lipid peroxidation and protein oxidation were significantly increased in the hippocampus and cerebellum of ethanol-exposed rats, and there was a concomitant reduction in the levels of the endogenous antioxidant glutathione. Voluntary exercise was able to reverse the deficits in glutathione both in ethanol-exposed males and females. Thus, while voluntary physical exercise increased glutathione levels in both sexes, its effects at the behavioral level were sex dependent, with only ethanol-exposed male runners showing a decrease in depressive-like behaviors.
Three Job-related Stress Models and Depression: a Population-based Study
Social Psychiatry and Psychiatric Epidemiology. Feb, 2012 | Pubmed ID: 21234534
To estimate the current prevalence of major depression in a sample of working population, and to examine the associations between job strain, effort-reward imbalance and family-work conflicts and major depression.
Health Behaviors Among Cancer Survivors Receiving Screening Mammography
American Journal of Clinical Oncology. Feb, 2012 | Pubmed ID: 21293247
The purpose of this study was to evaluate the prevalence of cancer-related behavioral risk factors among female cancer survivors, relative to women without a previous diagnosis of cancer.
Web-based Intervention for Adolescent Nonsmokers to Help Parents Stop Smoking: a Pilot Feasibility Study
Addictive Behaviors. Jan, 2012 | Pubmed ID: 21955873
A novel approach to tobacco control is to engage adolescent nonsmokers in support roles to encourage and help their parents stop smoking. This pilot study examined the feasibility and potential efficacy of a web-based support skills training (SST) intervention for adolescents to help a parent stop smoking. Forty nonsmoking adolescents 13-19 years of age (70% female, 93% White) were enrolled and randomly assigned to a health education (HE) control group (n=20) or SST (n=20). Both consisted of written materials and five weekly, 30 min, web-based, counselor-facilitated group sessions. Parents were enrolled for assessments only. Adolescents and parents completed assessments at baseline, week 6 (post-treatment), week 12 and 6-months follow-up. Both interventions were feasible based on treatment acceptability ratings, study retention and treatment compliance. The biochemically confirmed 6-month smoking abstinence rate was higher for parents linked to teens in HE (35%, 7/20) than in SST (10%, 2/20), p=0.13. About half of parents in each group reported a quit attempt since study enrollment. Teens can be engaged to help parents stop smoking. Future research is warranted on determining effective intervention approaches.
